RESUMO
Even though significant progress has been made, chemotherapy-induced emesis remains a challenging problem. Few studies focus on emesis in patients treated with carboplatin and the observation period is limited to the initial 24 h following chemotherapy. Thus, we investigated if tropisetron (T) monotherapy can adequately prevent acute and delayed emesis in non-small-cell lung cancer (NSCLC) patients receiving a moderately emetogenic chemotherapy (MEC) (carboplatin-containing) regimen. Furthermore, we explored the merits of adding dexamethasone (D) or alprazolam (A) to T, especially in the setting of a pre-existing high level of stress. We studied 60 patients with advanced NSCLC receiving carboplatin and taxanes in three consecutive cycles. During the first cycle, patients received 5 mg of T intravenously before chemotherapy and the same dose per os on each of the following 3 days. In the second cycle, T was co-administered with 8 mg of D once a day, while, during the third cycle, T was combined with per os A 0.25 mg every 12 h and continued over the following 3 days. Finally, we evaluated the impact of stress on the anti-emetic response achieved with the previously described regimens. The combination of T + A was superior to T monotherapy and the combination of T + D, regarding the prevention of acute and delayed emesis. Both T + A and T + D combinations led to appetite improvement, while patients receiving T + A experienced sedation more frequently. Interestingly, subgroup analysis revealed that patients without underlying stress obtained no further benefit by the addition of A or D, while both T + A and T + D combinations led to a better anti-emetic response in patients with stress. In conclusion, T monotherapy provides a satisfactory result in controlling nausea and emesis caused by a MEC regimen in patients without stress. However, the addition of D and, mainly, A improves its anti-emetic effect in patients with obvious stress.
Assuntos
Antieméticos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Indóis/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Alprazolam/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carboplatina/administração & dosagem , Quimioterapia Adjuvante , Dexametasona/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Psicológico , Taxoides/administração & dosagem , Resultado do Tratamento , Tropizetrona , Vômito/prevenção & controleRESUMO
PURPOSE: Cardiotoxicity associated with 5-fluorouracil (5FU) administration is infrequently reported in the literature, albeit case reports of acute coronary syndromes have been published. In the present study, patients undergoing 5FU chemotherapy were tested for the development of cardiac-related symptoms during its administration. PATIENTS AND METHODS: Five hundred twenty-two patients entered the study. Those experiencing any cardiac-related symptoms during 5FU infusion were subjected to electrocardiogram (ECG) and serum cardiac enzymes determination. If cardiotoxicity was confirmed, 5FU infusion was interrupted, sublingual nitrates administered and cardiac monitoring initiated, while patients with >2-fold enzyme elevation were admitted into a coronary care unit for at least 72 hours. Cases with acute myocardial infarction had to discontinue 5FU treatment. RESULTS: Overall 20 (3.8%) patients developed symptoms and/or ECG abnormalities due to 5FU. Patients with continuous 5FU infusion had a trend for higher incidence of cardiotoxicity (13/205, 6.3%) than the remaining (7/317, 2.2%; p=0.067). More specifically, increased toxicity was encountered in patients with continuous 24 h 5FU+ leucovorin (LV) infusion for 5 days compared to patients with the same schedule without LV (p <0.027) and patients with short 5FU+LV administration as well (p=0.024). Seven out of the 20 patients suffered acute myocardial infarction, 6 developed only ischemia, while ECG findings consistent with coronary vasospasm were detected in 4 patients and conduction disturbances in 3 patients (one subsequently died). CONCLUSION: The present study indicates a toxic effect of 5FU on myocardium, which is largely schedule-dependent. High level of alert is required when using this drug, while its toxic effect on the coronary endothelium and myocardium merits further investigation.
RESUMO
We examined the outcome of patients who developed breast cancer after curative chemotherapy (CHOP) for aggressive non-Hodgkin's lymphoma (NHL) in comparison to the outcome of a retrospectively selected matched-pair group of patients with de novo breast cancer, and evaluated the role of drug resistance-related protein (MDR, MRP, LRP) expression in breast cancer tissue. Twenty-two patients presented with breast cancer (BC) in complete remission after CHOP for NHL. The median age was 62 (49-70) years, each had high/intermediate grade B-cell NHL treated with 6 courses of CHOP, and were in complete remission. These patients were compared to a matched-pair group of de novo BC patients selected from our database over the same time period. Breast cancer tissue was stained by immunohistochemistry for drug resistance proteins LRP, MRP, and MDR. Breast cancer developed after a median of 26 (9-49) months of NHL diagnosis; breast tumor grades 1-2 were seen in 12, and grade 3 in 10 patients; 15 were negative and 7 weakly positive for estrogen and progesterone receptors. Twelve patients were stage IIIA/B, and 10 stage IV and were treated with conventional chemotherapy regimens. All progressed early in liver (n=13), brain (n=9), lung (n=6), bone (n=8), lymph nodes (n=7) and soft tissue (n=5), and received second-line chemotherapy with mitomycin-C + vinblastine or taxanes. The overall survival was 11.8 (6-26) months (p<0.01). Time from NHL to breast cancer development was 19 (14-27) months in patients with positive drug resistance proteins (group A), and 37 (26-56) months in patients with 1 or 2 positive resistance proteins (group B) (p<0.001). In patients with stage IIIA/B disease, there was no difference between the examined and control matched-pair group in median TTP, but there was in overall survival (OS) (23 vs 36 months, p=0.029). In advanced disease, there were more responders in the control vs the examined group (p=0.07). Patients in the control matched-pair group had more prolonged OS when compared to group A patients who developed BC in <24 months from NHL to BC (p=0.017). We conclude that breast cancer developing shortly after a complete response in NHL, is an aggressive disease variant with minimal potential for response to conventional chemotherapy. Analysis of drug resistance mechanisms concerning MDR, MRP and LRP indicates that most of these patients have BC that overexpress these proteins leading to the suggestion that these mechanisms might be a part of the aggressive disease phenotype and partially explain the poor outcome.
Assuntos
Neoplasias da Mama/complicações , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Linfoma não Hodgkin/complicações , Linfoma não Hodgkin/tratamento farmacológico , Subfamília B de Transportador de Cassetes de Ligação de ATP/análise , Subfamília B de Transportador de Cassetes de Ligação de ATP/metabolismo , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/diagnóstico , Quimioterapia Adjuvante , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Feminino , Humanos , Imunoquímica , Proteínas de Membrana Transportadoras/análise , Proteínas de Membrana Transportadoras/metabolismo , Pessoa de Meia-Idade , Proteína 2 Associada à Farmacorresistência Múltipla , Proteínas Associadas à Resistência a Múltiplos Medicamentos/análise , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Prednisona/uso terapêutico , Prognóstico , Proteínas Tirosina Fosfatases/análise , Proteínas Tirosina Fosfatases/metabolismo , Proteínas Tirosina Fosfatases Classe 4 Semelhantes a Receptores , Receptores de Superfície Celular/análise , Receptores de Superfície Celular/metabolismo , Estudos Retrospectivos , Vincristina/uso terapêuticoRESUMO
PURPOSE: To evaluate the efficacy and safety of irinotecan as second-line treatment in patients with advanced colorectal cancer (ACC) failing or relapsing after 5-fluorouracil (5-FU) plus leucovorin (LV) standard chemotherapy. PATIENTS AND METHODS: Irinotecan was randomly administered in two different schedules (once every 3 weeks, and every 10 days) in patients failing prior 5-FU plus LV. Patients were randomized to two treatment groups: group A received irinotecan 350 mg/m2 every 21 days and group B received irinotecan 175 mg/m2 days 1 and 10 every 21 days. RESULTS: Group A comprised 60 patients: 34 male/26 female, median age 64 years (range 48-70 years), and median Karnofsky performance status (PS) 90. Their metastatic sites included liver (n=47), lymph nodes (n=27), lung (n=14), abdomen (n=14), pelvis (n=8), "other" (n=2), and local recurrence (n=12). Group B comprised 60 patients: 36 male/24 female, median age 62 years (46-70 years), and median PS 90. Their metastatic sites included liver (n=49), lymph nodes (n=29), lung (n=17), abdomen (n=16), pelvis (n=11), "other" (n=2), and local recurrence (n=13). Group A showed the following responses: complete response (CR) 2, partial response (PR) 12, stable disease (SD) 21, progressive disease (PD) 26, overall response rate (ORR) 23%, tumor growth control 58%. Group B showed the following responses: CR 1, PR 14, SD 22, PD 23; ORR 25%; tumor growth control 62%. Toxicities included acute cholinergic syndrome (group A 53%, group B 19%; P<0.0001), late-onset diarrhea grade 1/2 (group A 21%, group B 46%) and grade 3/4 (group A 41%, group B 66%; P<0.0001), nausea and vomiting grade 1/2 (group A 34%, group B 59%) and grade 3/4 (group A 30%, group B 12%; P<0.0001), neutropenia grade 3/4 (group A 27%, group B 28%; P<0.03), with febrile neutropenia seen in only four patients in group A, anemia grade more than 2 (group A 28%, group B 12%; P<0.05), asthenia grade more than 3 (group A 24%, group B 18%; P<0.001), and alopecia grade more than 3 (group A 40%, group B 34%; P<0.2). CONCLUSIONS: . The present study indicates that, in patients with ACC who have relapsed after 5-FU plus LV, the administration of irinotecan fractionated into two doses every 21 days yields a similar efficacy to, but a much lower incidence of toxicity than, the same total dose of irinotecan administered once every 21 days.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Recidiva Local de Neoplasia , Inibidores da Topoisomerase I , Adenocarcinoma/enzimologia , Adenocarcinoma/mortalidade , Idoso , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/enzimologia , Neoplasias do Colo/mortalidade , Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/mortalidade , Progressão da Doença , Intervalo Livre de Doença , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intravenosas , Irinotecano , Avaliação de Estado de Karnofsky , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/enzimologia , Neoplasias Retais/mortalidadeRESUMO
In the present study, we evaluated the efficacy and safety of the weekly combination of etoposide, leucovorin (LV) and 5-fluorouracil (5-FU) when administered as second-line chemotherapy in patients with relapsed/refractory advanced colorectal cancer (ACC), previously treated with weekly LV+5-FU. Etoposide was administered at 3 different dose levels (DLs), in 3 groups of 20 patients each (total: 60); DL-I: etoposide 80 mg/m2, DL-II: etoposide 120 mg/m2, and DL-III: etoposide 180 mg/m2, in 45 min i.v. infusion, and followed in all levels by LV 100 mg/m2 i.v. over 1 hour and 5-FU 500 mg/m2 i.v. bolus. Treatment was administered weekly until disease progression or unacceptable toxicity. No patients at DL-I responded, while 2 patients at DL-II and 3 at DL-III had a partial response (PR). Stable disease (SD) rates were as follows; at DL-I: 2, DL-II: 8 and DL-III: 9. More patients in DL-I progressed (n = 19) compared to DL-II (n=10) and DL-II (n = 8) (p < 0.0007). Time to progression was for DL-I, -II, -III: 17, 15, and 14 weeks, respectively. Median survival was DL-I, -II, -III: 30, 30, and 32.5 weeks, respectively. Toxicity consisted mainly of neutropenia, diarrhea and mucositis at all DLs, and was significantly more severe in DL-III. No difference was noted in responses between DL-II and DL-III. The authors conclude that the combination of etoposide with LV+5-FU has limited activity when administered after failure of weekly LV+5-FU in patients with ACC and should not be recommended for further evaluation.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adenocarcinoma/mortalidade , Adenocarcinoma/patologia , Idoso , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Progressão da Doença , Etoposídeo/administração & dosagem , Estudos de Viabilidade , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Segurança , Terapia de Salvação , Taxa de SobrevidaRESUMO
Besides cytotoxicity, taxanes induce other biological effects, especially in the immune system. Taxanes have demonstrated immunostimulatory effects against neoplasms, supporting the idea that these agents suppress cancer through several mechanisms and not solely through inhibiting cell division. The purpose of the present study was to evaluate the effect of taxanes (paclitaxel and docetaxel) and investigate their ability in alterating important immunological parameters in breast cancer patients. Thirty women with advanced breast cancer undergoing chemotherapy were randomly assigned into two groups treated with either single agent Paclitaxel or Docetaxel. Sera from patients before the first and after the last treatment cycle and from normal donors were assayed by ELISA for IL-2, IL-1beta, IFN-gamma, GM-CSF, IL-6, TNF-alpha, and PGE2 levels. In these same blood samples, NK and LAK cell activity was tested in the total PBMC population against NK-sensitive K562 tumour targets, respectively, and autologous mixed lymphocyte reaction was tested by (3)H-thymidine proliferation assays. All patients in both groups responded to therapy. Significant differences were observed in the following immune parameters between the control group of healthy blood donors and the pretreatment values of both taxane groups; IL-2, GM-CSF, IFN-gamma levels and NK and LAK cell cytotoxicity were depressed, whereas TNF-alpha and IL-6 levels were raised in breast cancer patients before treatment compared to controls. There were no significant differences between the two treatment groups regarding any of the parameters studied. Both drugs led to increases in MLR values, NK and LAK cell cytotoxicity, and IL-6, GM-CSF, IFN-gamma levels, and decreases for IL-1, TNF, and PGE2 levels. The percentage of these differences was greater for docetaxel in comparison to paclitaxel (P<0.0001). More specifically, docetaxel demonstrated a more pronounced effect on enhancing MLR, NK, LAK activity and IFN-gamma, IL-2, IL-6, and GM-CSF levels, as well as caused more potent reduction in IL-1 and TNF-alpha levels when compared to paclitaxel. The present study indicates that patients responded to treatment of advanced breast cancer with single-agent paclitaxel or docetaxel leads to an increase in serum IFN-gamma, IL-2, IL-6, GM-CSF cytokine levels and enhancement of PBMC NK and LAK cell activity, while they both lead to a decrease of acute phase serum cytokine levels of IL-1 and TNF-alpha. Moreover, the effects of docetaxel are in all the above parameters more pronounced than those of paclitaxel.
Assuntos
Antineoplásicos Fitogênicos/imunologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/imunologia , Citocinas/análise , Substâncias de Crescimento/análise , Células Matadoras Ativadas por Linfocina/imunologia , Paclitaxel/análogos & derivados , Paclitaxel/imunologia , Taxoides , Adulto , Formação de Anticorpos/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/uso terapêutico , Citocinas/imunologia , Docetaxel , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Células Matadoras Ativadas por Linfocina/efeitos dos fármacos , Pessoa de Meia-Idade , Paclitaxel/farmacologia , Paclitaxel/uso terapêuticoRESUMO
The purpose of the present study was to investigate the association between performance status (PS) and mean dose of irinotecan (CPT-11) in patients with recurrent advanced colorectal cancer relapsing after 5-fluorouracil and leucovorin chemotherapy. Patients who had completed their last chemotherapy course with 5-fluorouracil and leucovorin for at least 6 weeks and progressed were included. Based on PS, we administered a starting dose of 250 mg/m(2) in patients with a PS 70-80 (group A), and 350 mg/m(2) for those with a PS > 80 (group B). Of a total of 90 treated patients, all were evaluable, 18 had a partial response (PR) (20%), 39 stable disease (43%), and 15 progressed (37%). No significant difference was noticed between patients with PS > or = 90 or < or = 80 (p = 0.925), or between those who received a mean dose of CPT-11 > or = 300 or < or = 300 (p = 0.602), for response, survival and time to progression. Toxicity was increased in group B as expected, with significant differences for acute cholinergic syndrome (p = 0.02), diarrhea after the first 24 h (p = 0.03) and severe diarrhea (p = 0.03). According to these results, we conclude that response to CPT-11 is independent of its dose, and that a dose of 250 mg/m(2) every 3 weeks might be a cost-effective and less toxic alternative in this setting. However, further adequately powered phase II or III randomized studies might be required in order to confirm this observation.
Assuntos
Antineoplásicos Fitogênicos/farmacologia , Camptotecina/farmacologia , Neoplasias do Colo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adulto , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Neoplasias do Colo/patologia , Análise Custo-Benefício , Custos de Medicamentos , Resistencia a Medicamentos Antineoplásicos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/farmacologia , Nível de Saúde , Humanos , Irinotecano , Leucovorina/administração & dosagem , Leucovorina/farmacologia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
PURPOSE: To evaluate efficacy of Raltitrexed, a specific thymidilate synthase inhibitor, in patients with advanced colorectal cancer (ACC) failing multiple prior chemotherapy regimens (e.g. 5-FU+LV, CPT-11, etc). METHODS: 20 patients with ACC; 13 males/7 females, median age 64 (range: 53-69), median Karnovsky PS: 80 (70-90), and sites of metastases; liver: 16, lung: 6, lymph nodes: 9, peritoneal: 8 and a life expectancy of at least 3 months, were entered in the present pilot study of Raltitrexed administration. All patients had progressed after prior chemotherapy with 5-FU+LV and subsequently CPT-11, and some had received further infusional 5-FU, Raltitrexed was administered at a dose of 3 mg/m2 i.v. every 21 days. RESULTS: 3 patients obtained stable disease (SID), 15%, with tumor marker decline (CEA, CA-19.9). Time-to-progression was 4.8 months (2.2-7) and survival 7.4 months (6.0-7.8). Toxicity was in general not severe and consisted mainly of myelosuppression; neutropenia (WHO) grade 2: 45% and grade 3: 22%, and anemia grade 1-2: 40%. CONCLUSION: Response to treatment with Raltitrexed is limited in patients with ACC failing multiple prior chemotherapy regimens, however, a limited percentage of patients with SD derived clinical benefit.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Inibidores Enzimáticos/uso terapêutico , Quinazolinas/uso terapêutico , Tiofenos/uso terapêutico , Timidilato Sintase/antagonistas & inibidores , Adenocarcinoma/secundário , Idoso , Antimetabólitos Antineoplásicos/toxicidade , Neoplasias Colorretais/patologia , Inibidores Enzimáticos/toxicidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Projetos Piloto , Quinazolinas/efeitos adversos , Tiofenos/efeitos adversosRESUMO
The relationship between polymyositis and malignancy is well known. Several types of tumors can be complicated with myositis and/or more frequently dermatomyositis. It has been suggested that tumors of the large bowel are rarely complicated by myositis. We describe a patient with adenocarcinoma of the colon presenting as polymyositis and review the available literature.
Assuntos
Adenocarcinoma/complicações , Neoplasias do Colo/complicações , Polimiosite/etiologia , Idoso , Feminino , HumanosRESUMO
BACKGROUND: Treatment options for patients with recurrent nonsmall cell lung carcinoma (NSCLC) remain limited as a result of poor activity of older agents after platinum-based therapy. In the current Phase II study, the authors evaluated the combination of gemcitabine and docetaxel in patients with recurrent NSCLC. METHODS: Patients with advanced NSCLC (Stage IIIB-IV), a World Health Organization performance status (PS) < or = 2, prior paclitaxel plus platinum-based chemotherapy, and unimpaired hematopoietic and organ function were eligible. Chemotherapy was administered as follows: gemcitabine 1000 mg/m(2) was administered on Days 1 and 8 followed by docetaxel 100 mg/m(2) on Day 8, and this regimen was recycled every 21 days. Prophylactic granulocyte-colony stimulating factor was administered on Days 10-14 or until the patient achieved a white blood cell count > or = 5000/microL. RESULTS: Of 43 patients who were entered on the study, 41 patients were evaluable for response, and all were evaluable for toxicity. The median patient age was 63 years (range, 47-70 years), the median PS was 1 (range, 0-2), there were 38 male patients, and there were 5 female patients. Four patients had Stage IIIA disease, 17 patients had Stage IIIB disease, and 22 patients had Stage IV disease. Histologies included 19 patients with adenocarcinoma, 18 patients with squamous cell carcinoma, and 3 patients with large cell carcinoma. Metastatic sites included lymph nodes in 28 patients, bone in 6 patients, liver in 5 patients, brain in 5 patients, lung nodules in 8 patients, adrenals in 7 patients, and other sites in 3 patients. All patients had received prior paclitaxel plus platinum-based treatment; 28 patients had received prior paclitaxel, ifosfamide, and cisplatin. Objective responses were partial response (PR) in 14 of 43 patients [33%; 95% confidence interval [95%CI], 18.5-46.6%], stable disease (SD) in 16 of 43 patients (37%; 95% CI, 22.8-51.6%), and progressive disease (PD) in 13 of 43 patients (30%; 95% CI, 16.3-43.7%). The median time to disease progression was 6 months (range, 1.0-20.0+ months), and the median survival was 8.5 months (range, 1.5-20.0+ months). The 1-year survival rate was 28%. Grade 3-4 neutropenia was experienced by 53% of patients (30% Grade 4), with 14% of patients experiencing febrile neutropenia. Grade 3 thrombocytopenia was experienced by 7% of patients (no Grade 4), whereas other Grade 3 nonhematologic toxicities were never encountered. CONCLUSIONS: The combination of gemcitabine and docetaxel is active and is well tolerated in patients with advanced NSCLC who have failed prior taxane plus platinum chemotherapy. This regimen represents a tolerable and effective combination to apply in the palliative treatment of patients with recurrent NSCLC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Desoxicitidina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Paclitaxel/análogos & derivados , Taxoides , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Docetaxel , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Cooperação do Paciente , Platina/uso terapêutico , Análise de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
Treatment options in patients with recurrent non-small-cell lung cancer (NSCLC) remain limited as a result of the poor activity of older agents after platinum-based therapy. The present phase II study aimed to evaluate the combination of gemcitabine and vinorelbine in patients with relapsed NSCLC after pretreatment with taxane+platinum-based regimens, since gemcitabine has demonstrated activity in that setting and the combination has been well tolerated in previous phase I/II studies. Patients with advanced NSCLC (stages III/IV), World Health Organization (WHO), Performance Status (PS) < or = 2, prior platinum+taxane-based chemotherapy and unimpaired haematopoietic and organ function were eligible. Chemotherapy was administered as follows: vinorelbine 25 mg/m(2) followed by gemcitabine 1000 mg/m(2), both administered on days 1 and 8, recycled every 3 weeks. 40 patients were entered and 39 were evaluable for response and all 40 for toxicity: median age was 61 years (range 50-72 years), median PS=1 (range 0-2), gender ratio=37 males/3 females, stages at initial diagnoses were IIIA=2, IIIB=14, IV=24. Metastatic sites included: lymph nodes: 23, bone: 4, liver: 5, brain: 4, lung nodules: 9, adrenals: 8, pleural effusion: 4. 22 patients had prior paclitaxel/ifosfamide/cisplatin treatment. Objective responses were; partial response (PR): 9/40 (22.5%), stable disease (SD): 13/40 (32.5%) and progressive disease (PD) 18/40 (45%). The median time-to-progression (TTP) was 4.5 months (range 1-17 months) and median survival 7 months (range 2-17+ months). 1-year survival was 17%. Grade 3 neutropenia was seen in 33% of patients. There was no grade 4 neutropenia and no episodes of febrile neutropenia. No grade 3/4 thrombocytopenia or grade 3/4 other non-haematological toxicities were observed. The combination of gemcitabine/vinorelbine is active and well tolerated in patients with advanced NSCLC failing prior taxane/platinum therapy. This regimen represents a tolerable and effective combination to apply in the palliative treatment of relapsed NSCLC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Vimblastina/análogos & derivados , Adulto , Idoso , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Feminino , Humanos , Ifosfamida/administração & dosagem , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Paclitaxel/administração & dosagem , Cooperação do Paciente , Análise de Sobrevida , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vinorelbina , GencitabinaRESUMO
The aim of the present randomized study was to evaluate which dose of Ondansentron (OND)(32 versus 8 mg) is appropriate for the antiemetic treatment of a uniform group of patients (pts) with Non Small Cell Lung Cancer (NSCLC) who were treated with Cisplatin (CDDP) 100 mg/m2 in combination with other less emetogenic drugs. One hundred and ten patients, with histologically confirmed NSCLC entered this randomized study. They were between 50 - 70 years old, with no previous Chemotherapy, with a PS (Karnofsky) >60%. They were randomized into two groups; Group A: OND as a 32 mg dose the first 24 hours, followed by 8 mg every 8 hrs for the following four days, combined with dexamethasone, 8 mg i.v. the first day, and 8 mg p.o., in the morning, the following three days. Group B: OND as a 8 mg dose every day for 4 days, combined with dexamethasone 8 mg i.v. and 8 mg p.o. the following three days. In this randomized study, of the 110 patients who entered, 106 were evaluable. Clinical parameters were similar between the examined groups. A higher number of patients of Group A presented complete response (P 0.0001), compared to patients of Group B who failed (P 0.004), during the first 24 hours. In the 3 days that followed, a higher number of pts of Group A presented complete response to the antiemetic therapy (P 0.001, P 0.0001), while Group B failed (P 0.007, P 0.001, P 0.019), or presented minor response (P 0.0001, P 0.004). Patients who had no antiemetic response needed additional therapy and were excluded from the evaluatio (13 pts of Group B). Retches (P 0.0001, P 0.005), and nausea (P 0.0001, P were also frequent in Group B. We concluded that reduced OND doses (8 mg) are inadequate in the prevention of emesis after high dose CDDP (100 mg/m2) and should be avoided.
Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Náusea/prevenção & controle , Ondansetron/uso terapêutico , Vômito/prevenção & controle , Idoso , Antieméticos/administração & dosagem , Antieméticos/efeitos adversos , Cisplatino/administração & dosagem , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitomicina/administração & dosagem , Náusea/induzido quimicamente , Ondansetron/administração & dosagem , Ondansetron/efeitos adversos , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vômito/induzido quimicamenteRESUMO
PURPOSE: The aim of the present phase II study was to evaluate the efficacy of the paclitaxel, ifosfamide, and cisplatin (PIC) combination in relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS: Eligible patients were those with SCLC who had progressed or relapsed after therapy with carboplatin and etoposide (with or without chest radiotherapy). The PIC regimen consisted of paclitaxel 175 mg/m(2) on day 1, ifosfamide 5 g/m(2) divided over days 1 and 2, and cisplatin 100 mg/m(2) divided over days 1 and 2; PIC was given every 21 days with granulocyte colony-stimulating factor support. RESULTS: Thirty-three patients (30 men and three women) were entered onto the study (median age, 62 years [range, 55 to 70 years]; median performance status, 1 [range, 0 to 2]). Metastatic sites at study entry included the lymph nodes (n = 13 patients), bone (n = 9), liver (n = 5), brain (n = 6), lung nodules (n = 8), adrenal glands (n = 9), and other (n = 2) Responses included eight complete remissions and 16 partial remissions (overall response rate, 73% [24 of 33 patients]). Five patients had stable disease and two had progressive disease. Median time to progression and overall survival were 21 and 28 weeks, respectively. The 1-year survival rate was 12%, with two patients alive without evidence of disease at 76 and 104 weeks since PIC initiation. Grade 3 and 4 toxicities included neutropenia in 30 patients (24 [73%] developed grade 4 neutropenia [ < 5 days]) and febrile neutropenia in six patients (18%); grade 3 or 4 thrombocytopenia was seen in nine patients (27%). No grade 3 neuropathy was observed; grade 1 or 2 CNS toxicity was seen in five patients, there was no renal toxicity, grade 2 myalgias were seen in nine patients, grade 2 diarrhea was seen in one patient, and grade 3 nausea or vomiting was seen in seven patients. There were no treatment-related deaths. CONCLUSION: In the present phase II study, the PIC combination seemed highly active and tolerable in patients with relapsed SCLC when it was administered as second-line treatment. Given the present experience, an evaluation of the PIC regimen as front-line treatment of SCLC is planned.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Metástase Neoplásica/tratamento farmacológico , Análise Atuarial , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cisplatino/administração & dosagem , Feminino , Grécia/epidemiologia , Humanos , Ifosfamida/administração & dosagem , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Recidiva , Taxa de SobrevidaRESUMO
We studied tropisetron (T) in patients with breast cancer receiving standard adjuvant chemotherapy with CEF (cyclophosphamide, epirubicin and 5-fluorouracil) over 3 consecutive cycles; T was administered alone or in combination with dexamethasone (D) or alprazolam (A). 50 women entered and during the 1st cycle patients received T i.v. before chemotherapy and the same dose orally on each of the following 3 days. In the 2nd cycle, T was administered together with D and during the 3rd cycle, T was combined with A and continued with T over the ensuing 3 days post-chemotherapy. Stress was present in 23 women and was evaluated for its impact on antiemetic response. Differences in the emetogenic response were found for nausea and vomiting mainly with the addition of A. The combination of T+A was superior to T and T+D in acute emesis (P<0.001). Concerning delayed emesis, differences were detected with both T+D and T+A (being equally effective) and superior to T alone (P<0.001). The emetogenic potential was decreased by the addition of A in comparison to T alone (P=0.001). Patients without stress had no difference, while patients with stress had a significantly better antiemetic result with the addition of D or A to T. In conclusion, T provides a satisfactory result in controlling nausea and emesis caused by moderately emetogenic CT regimens. Addition of D or A improves the antiemetic effect, and A provides better coverage in women with stress, a finding worth exploration in larger confirmatory studies.
Assuntos
Antieméticos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/tratamento farmacológico , Dexametasona/administração & dosagem , Indóis/uso terapêutico , Adulto , Alprazolam/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Fluoruracila/administração & dosagem , Humanos , Indóis/administração & dosagem , Pessoa de Meia-Idade , TropizetronaRESUMO
Dipyridamole, an inhibitor of nucleoside transport, increases the activity of 5-fluorouracil in a dose-dependent manner. The purpose of the present study was to determine whether dipyridamole with 5-fluorouracil and leucovorin gave an improved therapeutic outcome. Sixty patients entered in the present pilot study had previously received 5-fluorouracil (450 mg/m2) and leucovorin (100 mg/m2), every week, and relapsed during this treatment, which ended at least 6 weeks prior to study entry. Dipyridamole was administered at three different dosing schedules (DS) and methods of administration in three groups of patients. DS I: dipyridamole, 30 mg/m2 in normal saline solution, in 90 min iv infusion, followed by leucovorin, 100 mg/m2 iv push, followed by 5-fluorouracil, 450 mg/m2 in normal saline solution, in 60 min iv infusion, dipyridamole tablets (75 mg) every 12 hrs, continuously during the time of chemotherapy. DS II: dipyridamole, 50 mg/m2 in normal saline solution, in 90 min iv infusion, and the rest was the same as DS I. DS III: without oral dipyridamole, patients received dipyridamole (50 mg/m2) iv in the same manner as in DS I and II. Treatment was continued until tumor progression or unacceptable toxicity. All patients (n = 60) entered in the present study were assessable for response and toxicity. No complete response was observed. No patient at DS I responded, whereas 2 patients at DS II and 3 at DS III had a partial response (P <0.1). Stable disease was found with DS I (n = 1), DS II (n = 8) and DS III (n = 9) (P <0.01). More patients progressed at DS I (n = 19) than at DS II (n = 10) and DS III (n = 8) (P <0.0007). The median duration of response was 11 weeks (range, 8-16). Time to progression was 17 weeks for DS I, 15 weeks (range, 10-19) for DS II, and 14 weeks (range, 11-21) for DS III (P = 0.43). Median survival did not differ significantly between DS I (29 weeks; range, 14-48), DS II(31.5 weeks; range, 17-63) and DS III (36 weeks; range, 16-58) (P = 0.2). Neutropenia was most severe with DS I (grade 2, P<0.01) and DS II (grade 1, P<0.05) and nausea/vomiting with DS I (grade 0, P < 0.0005, grade 1, P <0.0002, grade 2, P <0.02) and DS III (grade 3, P<0.0009). Diarrhea was most severe in DS II (grade 3, P <0.005). Mucositis was increased in DS II (grade 0, P <0.008), anorexia in DS II (grade 0, P <0.032) and fatigue in DS I (grade 0, P <0.003). More patients in DS I than with the other two DS experienced headache (P <0.044). According to the response achieved at DS III (15% partial response and 45% stable disease) and the toxicity which was well tolerated mainly in this DS (except for nausea and vomiting grade 3, P <0.009), it can be stated that DS III is the appropriate dose and the simplest schedule of administration (administration of dipyridamole during therapy only). In conclusion, it appears that dipyridamole might still have a role in enhancing the clinical activity of drugs involved in the inhibition of the thymidylate synthetase biochemical pathway and its activity in combination with these agents (5-fluorouracil + leucovorin) as frontline treatment should therefore be explored in future phase II studies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Dipiridamol/administração & dosagem , Fluoruracila/administração & dosagem , Leucovorina/administração & dosagem , Idoso , Dipiridamol/efeitos adversos , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/farmacocinética , Humanos , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Projetos PilotoRESUMO
A 37-yr-old man who had undergone renal transplantation for end-stage renal failure presented with a large right pelvic mass obstructing the transplanted kidney. Initially, this was diagnosed as an anaplastic tumor while he had been on immunosuppressive treatment for kidney allograft rejection after transplantation. Despite difficulties of classic histopathology to reveal the origin of his tumor, FISH analysis revealed the presence of chromosome 12p abnormalities, strongly indicative of a germ-cell tumor-more likely seminoma-with extragonadal presentation. Because of renal dysfunction, he was treated with carboplatin (dose adjusted according to renal clearance) and etoposide, and when he experienced a rather atypical progression with bone metastases, he was treated with single-agent paclitaxel, and died almost 13 mo after initial presentation. The case adds further to the existing small list of seminoma/GCTs developing in transplant recipients, points to the unusual presentation patterns and diagnostic histopathology challenges, and presents the difficulty in therapeutic options, as a result of frequent renal dysfunction and intercurrent immunosuppressive therapy. All of these issues together with an extensive literature review are discussed in detail.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Falência Renal Crônica/terapia , Transplante de Rim , Neoplasias Pélvicas/tratamento farmacológico , Neoplasias Pélvicas/etiologia , Seminoma/tratamento farmacológico , Seminoma/etiologia , Adulto , Neoplasias Ósseas/secundário , Carboplatina/administração & dosagem , Aberrações Cromossômicas , Cromossomos Humanos Par 12/genética , Diagnóstico Diferencial , Progressão da Doença , Etoposídeo/administração & dosagem , Evolução Fatal , Humanos , Masculino , Paclitaxel/administração & dosagem , Neoplasias Pélvicas/diagnóstico , Seminoma/diagnósticoRESUMO
The outcome of treatment of advanced renal cell carcinoma is disappointing. In interferon (IFN)-treated patients, the high incidence of adverse effects causes many patients to withdraw from treatment. This 12-week randomized study compared the incidence of toxicity associated with high-dose IFN monotherapy (15 x 10(6) U thrice weekly) and treatment with the combination of low-dose IFN (5 x 10(6) U thrice weekly) and 6 mg/m2 vinblastine (VBL) every 14 days in 100 consecutive patients. There was no significant difference in response rate between treatment arms (42% IFN vs. 34% IFN + VBL) or between subgroups (by tumor location). Combined treatment was associated with a significantly lower incidence of fever, fatigue, and weight loss but with a higher incidence of leukopenia. There was no significant difference in the incidence of other events. More patients treated with IFN monotherapy required bed rest, and overall treatment costs were 60% higher than for combined treatment. It is concluded that combined treatment with low-dose IFN and VBL, without loss of short-term efficacy, is better tolerated and less expensive than high-dose IFN monotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Interferon-alfa/administração & dosagem , Interferon-alfa/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Adulto , Idoso , Antineoplásicos Fitogênicos/administração & dosagem , Antineoplásicos Fitogênicos/efeitos adversos , Antineoplásicos Fitogênicos/economia , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Carcinoma de Células Renais/secundário , Custos e Análise de Custo , Tolerância a Medicamentos , Fadiga/induzido quimicamente , Feminino , Febre/induzido quimicamente , Humanos , Interferon alfa-2 , Interferon-alfa/economia , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Vimblastina/economia , Redução de Peso/efeitos dos fármacosRESUMO
The purpose of this study was to determine whether ondansentron given to patients with non-small-cell lung cancer (NSCLC) undergoing cisplatin-based chemotherapy, has better antiemetic activity administered every 6 or 8 h in controlling cisplatin-induced emesis. All patients had previously received 3 cycles of cisplatin-based chemotherapy at a dose of 100 mg/m(2). Ondansentron was given according to two schedules in group A (50 patients) at a dose of 8 mg in 100 ml normal saline over 10 min i.v. infusion, together with dexamethasone 8 mg before the infusion of cisplatin, continued with both drugs at the same dose and administration after 8 and 16 h; in group B (50 patients) both drugs were administered before the infusion of cisplatin, continued after 6, 12 and 18 h. During the next 3 days, patients continued with tablets of dexamethasone 4 mg and ondansentron 8 mg, group A every 8 h, and group B every 6 h. The only difference in terms of antiemetic response that was noticed between the two groups was the number of patients experiencing nausea which was found increased in group A (n = 32) in comparison to group B (n = 25) (p < 0.022). No difference was noticed in the number of vomiting episodes and retches or emesis control, during the 3-day evaluation period after cisplatin infusion or in side effects. In conclusion, the total dose of 24 mg ondansentron during the acute phase of emesis is as effective as the total dose of 32 mg.
Assuntos
Antieméticos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/efeitos adversos , Dexametasona/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Ondansetron/administração & dosagem , Vômito Precoce/prevenção & controle , Adulto , Idoso , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The necessity to develop more effective chemotherapy regimens in advanced nonsmall cell lung carcinoma (NSCLC) prompted the authors to evaluate the paclitaxel-ifosfamide-cisplatin (PIC) combination, developed on the basis of high individual single-agent activity, in vitro synergism, and tolerance as determined in a previous Phase I study by the authors. PATIENTS: Eligibility criteria included advanced NSCLC (American Joint Committee on Cancer [AJCC]/International Union Against Cancer [UICC] Stage III/IV), Eastern Cooperative Oncology Group performance status (PS) = 2, no prior chemotherapy, and unimpaired hematopoietic and organ function. Chemotherapy included, paclitaxel 175 (in the first 10 patients) or 200 mg/m(2) on Day 1, ifosfamide: 5 g/m(2) divided over Days 1 and 2, and cisplatin 100 mg/m(2) divided over Days 1 and 2, recycled every 21 days. Granulocyte-colony stimulating factor was administered from Day 4 to 13 or until leukocyte count reached >/= 10,000/microL. RESULTS: Fifty patients were entered, and all were evaluable for response and toxicity: median age, 58 years (range, 40-72), PS, 1 (range, 0-2), Gender: 44 males and 6 females, Stages IIIA, 6 patients; IIIB, 17; IV, 27; histologies: adenocarcinoma, 27 patients; squamous, 17; large cells, 5; unspecified, 1. Metastatic sites at diagnosis included lymph nodes, 33 patients; bone, 6; liver, 5; brain, 10; lung nodules, 7; adrenals, 6; other, 2. Thirty-two of 50 (64%; confidence interval, 50.7-77.3%) evaluable patients responded: 4 complete remissions, 28 partial remissions, 13 stable disease, and 5 progressive disease. The quality-of-life score improved in 37 of 50 (74%) patients. The median response duration was 7 months (range 2-34+); median time-to-progression, 8 months (range, 1-36+), median overall survival, 12 months (range, 2-36+). One-year survival was 53%. Grade 3 and 4 toxicities included neutropenia 38 of 50 patients with 21 developing Grade 4 neutropenia (= 5 days) and 7 of these febrile neutropenia (14%); thrombocytopenia, 4 of 50 patients with 1 Grade 4 requiring platelet transfusions, 1 Grade 3 neuropathy; Grade 1-2 central nervous system toxicity due to ifosfamide was seen in 22 patients, no renal toxicity, 15 Grade 2 myalgias, 17 Grade 2 diarrhea, and 10 Grade 3 vomiting. CONCLUSIONS: The PIC combination appears highly active and tolerable in advanced NSCLC administered in the outpatient setting. Future randomized comparisons to other current standard regimens in NSCLC will be warranted.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Feminino , Humanos , Ifosfamida/administração & dosagem , Ifosfamida/efeitos adversos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Cooperação do Paciente , Análise de Sobrevida , Resultado do TratamentoRESUMO
Some factors have demonstrated an influence on emesis and antiemetic response. In order to study these factors, 306 patients (pts) entered this study receiving cisplatin based combination chemotherapy (CT) (100 mg/m3, with ondansetron (8 mg, 3 times daily for 4 days) as the only antiemetic treatment. Known factors that influence the result of antiemetic therapy such as age, sex, performance status (Karnofsky), site of primary tumor, weight loss, anxiety, depression, psychological problems related to CT (psychological PRC) etc, were included in the evaluation. We evaluated the number of vomits, retches and nausea. The existence of psychological PRC was found to be a prominent factor for the development of nausea and emesis, being at the same time strongly associated with scaling variables (Gralla, retching and nausea grading) used to measure the severity of nausea and emesis (p = 0.001). Stress was also a significant predictor; patients with stress had an almost two times higher probability to develop nausea or retching compared to patients without stress indications (p = 0.001), while the occurrence of retching was marginal. Younger patients (less than 40 years old) were found to be almost three times more susceptible to retching compared to older patients (more than 40 years old) (P 0.006). With all possible evaluations, we concluded that significant factors are psychological PRC, stress and age. In conclusion, three factors, age, stress and psychological PRC, should be taken seriously into consideration in the design of future trials evaluating antiemetic treatment, as well as in the every-day clinical practice, in order to provide patients with a better quality of life during emetogenic CT.