RESUMO
PURPOSE: Previous studies suggest tetracycline and other antibiotics lessen the severity of epidermal growth factor receptor (EGFR) inhibitor-induced rash. This study sought to confirm such findings. METHODS: Patients starting an EGFR inhibitor were eligible for this randomized, double-blinded, placebo-controlled study and had to be rash-free. They were then randomly assigned to tetracycline 500 mg orally twice a day for 28 days versus a placebo. Rash development and severity (monthly physician assessment and weekly patient-reported questionnaires), quality of life (SKINDEX-16), and adverse events were monitored during the 4-week intervention and then for an additional 4 weeks. The primary objective was to compare the incidence of grade 2 or worse rash between study arms; 32 patients per group provided a 90% probability of detecting a 40% difference in incidence with a type I error rate of 0.05 (two-sided). RESULTS: Sixty-five patients were enrolled, and groups were balanced on baseline characteristics. During the first 4 weeks, healthcare provider-reported data found that 27 tetracycline-treated patients (82%) and 24 placebo-exposed patients (75%) developed a rash. This rash was a grade 2+ in 17 (52%) and 14 (44%), respectively (p = 0.62). Comparable grade 2+ rash rates were observed during weeks 5 through 8 as well as with patient-reported rash data throughout the study period. Quality of life was comparable across study arms, and tetracycline was well tolerated. CONCLUSION: Although previous studies suggest otherwise, this randomized, double-blinded, placebo-controlled study did not find that tetracycline lessened rash incidence or severity in patients who were taking EGFR inhibitors.
Assuntos
Antineoplásicos/efeitos adversos , Toxidermias/prevenção & controle , Receptores ErbB/antagonistas & inibidores , Tetraciclina/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Método Duplo-Cego , Toxidermias/etiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Índice de Gravidade de DoençaRESUMO
BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a troublesome chronic symptom that has no proven pharmacologic treatment. The purpose of this double-blind randomized placebo-controlled trial was to evaluate a novel compounded topical gel for this problem. METHODS: Patients with CIPN were randomized to baclofen 10 mg, amitriptyline HCL 40 mg, and ketamine 20 mg in a pluronic lecithin organogel (BAK-PLO) versus placebo (PLO) to determine its effect on numbness, tingling, pain, and function. The primary endpoint was the baseline-adjusted sensory subscale of the EORTC QLQ-CIPN20, at 4 weeks. RESULTS: Data in 208 patients reveal a trend for improvement that is greater in the BAK-PLO arm over placebo in both the sensory (p = 0.053) and motor subscales (p = 0.021). The greatest improvements were related to the symptoms of tingling, cramping, and shooting/burning pain in the hands as well as difficulty in holding a pen. There were no undesirable toxicities associated with the BAK-PLO and no evidence of systemic toxicity. CONCLUSION: Topical treatment with BAK-PLO appears to somewhat improve symptoms of CIPN. This topical gel was well tolerated, without evident systemic toxicity. Further research is needed with increased doses to better clarify the clinical role of this treatment in CIPN.
Assuntos
Amitriptilina/uso terapêutico , Baclofeno/uso terapêutico , Ketamina/uso terapêutico , Doenças do Sistema Nervoso Periférico/tratamento farmacológico , Administração Cutânea , Inibidores da Captação Adrenérgica/administração & dosagem , Inibidores da Captação Adrenérgica/efeitos adversos , Inibidores da Captação Adrenérgica/uso terapêutico , Idoso , Amitriptilina/administração & dosagem , Amitriptilina/efeitos adversos , Antineoplásicos/efeitos adversos , Baclofeno/administração & dosagem , Baclofeno/efeitos adversos , Método Duplo-Cego , Combinação de Medicamentos , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Antagonistas de Aminoácidos Excitatórios/efeitos adversos , Antagonistas de Aminoácidos Excitatórios/uso terapêutico , Feminino , Agonistas dos Receptores de GABA-B/administração & dosagem , Agonistas dos Receptores de GABA-B/efeitos adversos , Agonistas dos Receptores de GABA-B/uso terapêutico , Géis , Humanos , Ketamina/administração & dosagem , Ketamina/efeitos adversos , Lecitinas/química , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Poloxâmero/química , Resultado do TratamentoRESUMO
PURPOSE: This study assessed whether maintenance therapy with carboxyaminoimidazole (CAI), compared to placebo, prolonged overall survival in stage IIIB/IV NSCLC patients who had tumour regression or stable disease after treatment with one chemotherapy regimen. METHODS: After completion of chemotherapy, patients were randomized to receive daily oral CAI at 250mg or placebo. Treatment continued until patient refusal, disease progression or unacceptable adverse event (AE). Quality of life (QOL) was assessed by UNISCALE and Functional Assessment of Cancer Therapy for Lung Cancer (FACT-L). RESULTS: Registration was halted early for slow accrual (targeted 360, randomized 186: 94 CAI, 92 placebo). All patients were off active treatment at time of analyses. Non-haematologic AEs (primarily grade 1, 2) observed significantly more often in the CAI group included fatigue (54.5% versus 29.3%), anorexia (31.1% versus 13.0%), nausea (62.2% versus 30.4%), vomiting (32.2% versus 14.1%), neurosensory (60.0% versus 44.6%) and ataxia (33.3% versus 16.3%). Patients discontinued treatment for AEs, death on study or refusal more often in the CAI group (36.0% versus 8.7%, p<0.0001). No significant differences in survival or time to progression were observed (median: CAI versus placebo: 11.4 months versus 10.5 months, log rank p=0.54; 2.8 months versus 2.4 months, log rank p=0.50). More patients receiving CAI reported a clinically significant (10-point) decline in QOL particularly on the functional (58% versus 37%, p=0.05) construct of FACT-L and UNISCALE (72% versus 51%, p=0.04). CONCLUSION: The addition of CAI following chemotherapy does not provide clinical benefit or improvement in QOL over placebo in advanced NSCLC.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Triazóis/uso terapêutico , Idoso , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Método Duplo-Cego , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Placebos , Qualidade de VidaRESUMO
BACKGROUND: Levamisole combined with 5-fluorouracil (5-FU) was previously shown to significantly reduce tumor relapses and improve patient survival when given postoperatively in patients with resected stage III colon cancer. Laboratory investigations subsequently documented a direct dose-dependent enhancement of 5-FU cytotoxicity with increasing concentrations of levamisole against human cancer cell lines. A clinical trial was designed to test the value of levamisole given at its maximum tolerated dose in combination with 5-FU-based chemotherapy. PATIENTS AND METHODS: Eight hundred seventy-eight patients who had undergone complete surgical resection of high-risk stage II/III colon cancer were stratified by known prognostic factors and randomized to receive 1 of 2 treatment regimens: standard-dose levamisole combined with 5-FU and leucovorin; or high-dose levamisole combined with the same chemotherapy. Serum neopterin was monitored in a cohort of patients to evaluate immune function. RESULTS: Severe vomiting and neurologic side effects required reduction in the dose of levamisole that could be safely administered on the high-dose levamisole regimen. There were no significant differences in disease-free survival, overall survival, or levels of serum neopterin between the treatment regimens. CONCLUSION: It was not possible to improve the efficacy of surgical adjuvant chemotherapy for patients with high-risk colon cancer by giving levamisole at its maximum tolerated dose in combination with 5-FU and leucovorin. High rates of severe gastrointestinal and neurologic side effects were observed with the high-dose levamisole regimen.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Neoplasias do Colo/sangue , Neoplasias do Colo/mortalidade , Neoplasias do Colo/cirurgia , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Levamisol/administração & dosagem , Levamisol/efeitos adversos , Masculino , Pessoa de Meia-Idade , Neopterina/sangueRESUMO
BACKGROUND: Older patients, even if fit, are often considered incapable of tolerating platinum-based systemic therapy. We performed a retrospective analysis of Eastern Cooperative Oncology Group (ECOG) 5592, a phase III randomized trial of platinum-based chemotherapy regimens for non-small-cell lung cancer (NSCLC), and compared outcomes in enrollees 70 years of age and older with those in younger patients. METHODS: ECOG carried out a randomized phase III trial of cisplatin plus either etoposide or paclitaxel in chemotherapy-naïve NSCLC patients with stages III(B) or IV disease. Toxic effects, response rates, and survival rates were compared between age groups. All P values were two-sided. RESULTS: A total of 574 patients enrolled from August 1993 through December 1994 were evaluable. Eighty-six (15%) were 70 years old or older. Older patients had a higher incidence of cardiovascular (P =.009) and respiratory (P =.04) comorbidities and nonanalgesic medication use (P =.02). Leukopenia (P<.001) and neuropsychiatric toxicity (P =.002) were more common in elderly men than in younger men. Elderly women lost more weight than younger women (P =.006). Other toxic effects were similar in older and younger patients. The proportions with clinical partial or complete response (21.5% versus 23.3%; Fisher's exact test, P =.66), median time to progression (4.37 versus 4.30 months; log-rank test, P =.29), and survival distribution (log-rank test, P =.29; median survival, 9.05 versus 8.53 months; 1-year survival, 38% versus 29%; and 2-year survival, 14% versus 12%) were similar in patients younger than 70 years and 70 years old or older. Baseline quality-of-life and treatment-outcome indices were similar. Equivalent declines over time in functional well-being occurred in both groups. CONCLUSION: Response rate, toxicity, and survival in fit, elderly NSCLC patients receiving platinum-based treatment appear to be similar to those in younger patients, although patients 70 years old or older have more comorbidities and can expect more leukopenia and neuropsychiatric toxicity. Advanced age alone should not preclude appropriate NSCLC treatment.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Etoposídeo/efeitos adversos , Etoposídeo/uso terapêutico , Feminino , Humanos , Masculino , Paclitaxel/efeitos adversos , Paclitaxel/uso terapêutico , Qualidade de Vida , Distribuição Aleatória , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the effect of postoperative paclitaxel and cisplatin on 2-year survival in patients with completely resected adenocarcinoma of the distal esophagus, gastro-esophageal (GE) junction, and cardia. PATIENTS AND METHODS: We conducted a multicenter phase II trial. Patients had pathologically staged T2 node-positive to T3-4, any node status adenocarcinoma of the distal esophagus, GE junction, or gastric cardia with negative margins (R0). Treatment consisted of four cycles of paclitaxel 175 mg/m2 intravenously (i.v.) over 3 hours followed by cisplatin 75 mg/m2 i.v. every 21 days. A positive outcome was considered to be an improvement in 2-year survival rate by > or = 20% compared to historic controls. RESULTS: Fifty-nine patients were recruited from 20 centers. Of 55 eligible patients, 49 (89%) had lymph node involvement. Forty-six patients (84%) completed all four cycles. Of the total 59 patients, 31 (56%) developed grade 3 or 4 toxicity with leukopenia/neutropenia, nausea/vomiting, and metabolic toxicities were most common. The median follow-up for surviving patients was 4 years. At 2 years, 33 patients were alive and 22 were dead, with a survival rate of 60% (95% CI, 46% to 73%; one-sided P = .0008 compared with the historic controls). CONCLUSION: Our data suggest that adjuvant paclitaxel and cisplatin may improve survival in R0 resected patients with locally advanced adenocarcinoma of the distal esophagus, GE junction, and cardia. These results warrant further testing in randomized trials.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Esofágicas/tratamento farmacológico , Adenocarcinoma/cirurgia , Adulto , Idoso , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Neoplasias Esofágicas/cirurgia , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: Gemcitabine is generally considered to constitute first-line therapy for pancreatic cancer. To determine whether the addition of fluorouracil (5-FU) improves on the results from single-agent gemcitabine, the Eastern Cooperative Oncology Group (ECOG) compared gemcitabine plus bolus 5-FU with gemcitabine alone for patients with advanced pancreatic carcinoma. PATIENTS AND METHODS: This trial involved patients with biopsy-proven, advanced carcinoma of the pancreas not amenable to surgical resection. Patients were randomized to receive either gemcitabine alone (1,000 mg/m(2)/wk) weekly for 3 weeks of every 4 or to receive gemcitabine (1,000 mg/m(2)/wk) followed by 5-FU (600 mg/m(2)/wk) weekly on the same schedule. The primary end point of the trial was survival, with secondary end points of time to progression and response rate. RESULTS: Of 327 patients enrolled over 18 months, 322 were eligible. Overall, the median survival was 5.4 months for gemcitabine alone and 6.7 months for gemcitabine plus 5-FU (P =.09). Progression-free survival for gemcitabine alone was 2.2 months, compared with 3.4 months for gemcitabine plus 5-FU (P =.022). Objective responses were uncommon and were observed in only 5.6% of patients treated with gemcitabine and 6.9% of patients treated with gemcitabine plus 5-FU. Most toxicities were hematologic or gastrointestinal; no significant differences were noted between the two treatment arms. CONCLUSION: 5-FU, administered in conjunction with gemcitabine, did not improve the median survival of patients with advanced pancreatic carcinoma compared with single-agent gemcitabine. Further studies with other combinations of gemcitabine and 5-FU are not compelling, and clinical trial resources should address other combinations and novel agents.
Assuntos
Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Fluoruracila/administração & dosagem , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estatísticas não Paramétricas , Análise de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
PURPOSE: A pressing need exists for agents active against anthracycline- or taxane-refractory metastatic breast cancer (MBC), or both. Previous clinical trials suggested that irinotecan might have such activity. We conducted this multicenter phase II study to assess efficacy and tolerability of two irinotecan schedules. PATIENTS AND METHODS: MBC patients who experienced disease progression after one to three chemotherapy regimens, including at least one anthracycline- or taxane-based regimen, were randomly assigned to irinotecan in 6-week cycles comprising 100 mg/m(2) weekly for 4 weeks, then a 2-week rest (weekly) or 240 mg/m(2) every 3 weeks. RESULTS: The weekly arm had 52 assessable patients; the every-3-weeks arm had 51 assessable patients. In the weekly arm, the objective response (complete regression [CR] + partial regression [PR]) rate was 23% (one CR, 11 PR; 95% CI, 13% to 37%). Median response duration was 4.9 months (range, 1.9 to 15.9 months), and median overall survival was 9.7 months (95% CI, 8.0 to 14.2 months). In the every-3-weeks arm, the objective response rate was 14% (nine PR; 95% CI, 6% to 26%), median response duration was 4.2 months (range, 3.1 to 13.9 months), and median overall survival was 8.6 months (95% CI, 7.0 to 12.3 months). Treatment generally was well tolerated, especially in the weekly arm. Grade 3 to 4 adverse events with > or = 10% incidence included neutropenia (29%) and diarrhea (17%) in the weekly arm and neutropenia (36%), vomiting (20%), dyspnea (18%), nausea (16%), and diarrhea (12%) in the every-3-weeks arm. CONCLUSION: Irinotecan is active with good tolerability in refractory MBC. Irinotecan (especially weekly) warrants additional study as monotherapy and in combination regimens in this setting.
Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Camptotecina/análogos & derivados , Camptotecina/administração & dosagem , Adulto , Antraciclinas/uso terapêutico , Neoplasias da Mama/patologia , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Irinotecano , Metástase Neoplásica , Estadiamento de Neoplasias , Estudos Prospectivos , Análise de Sobrevida , Taxoides/uso terapêutico , Resultado do TratamentoRESUMO
PURPOSE: To evaluate the value of thymidylate synthase (TS), Ki-67, and p53 as prognostic markers in patients with Dukes' B2 and C colon carcinoma. METHODS: We conducted a retrospective analysis to evaluate the prognostic value of TS, Ki-67, and p53 in 465 patients with Dukes' B2 (220 patients) or Dukes' C (245 patients) colon carcinoma. Patients represent a nonrandom subset obtained from five randomized phase III trials and were treated with either surgery alone (151 patients) or surgery plus fluorouracil-based chemotherapy (314 patients). All three markers were assayed using immunohistochemical techniques. RESULTS: With a minimum follow-up of 5 years, our retrospective analysis failed to demonstrate a consistent and significant association between TS, Ki-67, or p53 and either disease-free survival or overall survival. Exploratory analyses did not reveal a convincing explanation for these results that are in conflict with the published literature. Notable interactions were observed. In particular, high Ki-67 levels were associated with increased (decreased) survival in patients with low (high) TS intensity. Patients whose tumors stained positively for p53 seemed to benefit substantially from the use of adjuvant chemotherapy compared with those who were not treated (P =.05). CONCLUSION: This retrospective investigation failed to demonstrate a significant association between TS, Ki-67, or p53 staining and clinical outcome.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias do Colo/química , Antígeno Ki-67/análise , Timidilato Sintase/análise , Proteína Supressora de Tumor p53/análise , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Colectomia , Neoplasias do Colo/enzimologia , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Neoplasias do Colo/terapia , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Análise de SobrevidaRESUMO
PURPOSE: To evaluate quality of life (QOL) and tumor response after administration of an oral chemotherapy regimen in patients with previously untreated metastatic colorectal cancer. PATIENTS AND METHODS: Seventy-eight patients received a mean number of 5.8 cycles of therapy. QOL data were analyzed at baseline, after every two cycles of therapy, and at the time of treatment discontinuation. The Uniscale and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire C30 were both utilized. RESULTS: The confirmed response rate was 26% (95% confidence interval [CI], 17% to 37%). Median survival was 11.3 months (95% CI, 9.6 to 15.1 months). Global QOL scores were unchanged over the course of therapy by either tool. Only the physical function subscale score had worsened at the end of therapy. In an analysis of responding patients, significant and durable improvements in both global QOL measures as well as select subscale scores were observed. Diarrhea and physical function QOL scores had declined at the time of treatment discontinuation. Patients who did not respond to therapy had preserved QOL scores when they were evaluated after two cycles of therapy. CONCLUSION: This oral treatment strategy preserved QOL in treated patients. Global QOL measures as well as several QOL subscale scores significantly improved in patients with a documented response to therapy. The profile of improved QOL components indicated that patient well-being was related to tumor response in specific and perceivable ways. Nonresponding patients reported preserved QOL during the first two cycles of therapy. QOL analysis was feasible and informative in this moderately sized multicenter phase II trial.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Qualidade de Vida , Administração Oral , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Although 5-fluorouracil (5-FU)-based chemotherapy is commonly used in patients with advanced colorectal cancer (CRC), little data exist on the tolerability and benefit of therapy in elderly patients. To compare toxicity, dose intensity, response rate, time to tumor progression, and overall survival for older and younger patients, we conducted a pooled analysis of 1748 patients, divided into 4 quartile-based age groups, from 4 North Central Cancer Treatment Group trials testing 5-FU with or without leucovorin for advanced CRC. Patients aged > 65 years had modestly higher rates of severe toxicity (grade >/= 3) overall (53% vs. 46%) and higher rates of diarrhea (21% vs. 16%), stomatitis (17% vs. 13%), and infection (4% vs. 2%). Toxicity rates were similar between patients aged 66-70 years and patients aged > 70 years. The response rate did not differ by age group (2-sided; P = 0.90); it was significantly lower for patients with higher performance status scores (30% for score of 0/1; 17% for 2/3; 2-sided; P = 0.001). Performance status, not age, was predictive of time to tumor progression and overall survival. The older patients with CRC treated with 5-FU have modestly higher rates of severe toxicity, mainly diarrhea and stomatitis. Supportive measures to control diarrhea and stomatitis may be particularly important in elderly patients. Age alone should not be used to determine whether older patients are treated, because performance status is predictive of dose intensity, response rate, time to tumor progression, and overall survival.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Fluoruracila/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/efeitos adversos , Distribuição de Qui-Quadrado , Ensaios Clínicos como Assunto , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Fluoruracila/efeitos adversos , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Análise de Sobrevida , Resultado do TratamentoRESUMO
PURPOSE: This Phase III study was performed to determine whether chemotherapy plus b.i.d. or q.d. radiotherapy (RT) resulted in superior survival for patients with Stage III non-small-cell lung cancer (NSCLC). METHODS AND MATERIALS: Patients with Stage III NSCLC and an Eastern Cooperative Oncology Group performance status of Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
, Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico
, Carcinoma Pulmonar de Células não Pequenas/radioterapia
, Neoplasias Pulmonares/tratamento farmacológico
, Neoplasias Pulmonares/radioterapia
, Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem
, Carcinoma Pulmonar de Células não Pequenas/patologia
, Carcinoma de Células Escamosas/tratamento farmacológico
, Carcinoma de Células Escamosas/patologia
, Carcinoma de Células Escamosas/radioterapia
, Cisplatino/administração & dosagem
, Etoposídeo/administração & dosagem
, Feminino
, Seguimentos
, Humanos
, Neoplasias Pulmonares/patologia
, Masculino
, Estudos Prospectivos
, Radioterapia/efeitos adversos
, Dosagem Radioterapêutica
, Análise de Sobrevida
RESUMO
PURPOSE: Before now oral vinorelbine has not yet been tested in a cohort of elderly, advanced non-small cell lung cancer patients, even though the intravenous form of this drug provides a reasonable therapeutic option for this group. This trial was conducted to determine the tumor response rate and toxicity profile of oral vinorelbine in advanced non-small cell lung cancer patients > or = 65 years of age. PATIENT AND METHODS: Fifty-eight evaluable patients > or = 65 years of age with advanced non-small cell lung cancer were enrolled. Median age was 73 years (range: 65-87). The Eastern Cooperative Oncology Group (ECOG) performance score was 0, 1, or 2 in 29, 59, and 12% of patients, respectively. All patients had adequate organ function. Oral vinorelbine 60 mg/m2 per week was prescribed weekly as first-line therapy. RESULTS: Two patients manifested a confirmed tumor response, yielding a response rate of 3.4% (95% confidence interval (CI): 0.4, 11.9%). There were no complete responses. Median progression-free survival was 3.5 months (95% CI: 2.2, 5.4 months), and median overall survival was 7.5 months (95% CI: 5.0, 12 months). There were five deaths, one of which might have been treatment-related, and there were 10 grade 4 events. CONCLUSIONS: Oral vinorelbine, as prescribed in this trial, provides minimal activity in the treatment of advanced non-small cell lung cancer in patients > or = 65 years of age.
Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Vimblastina/análogos & derivados , Vimblastina/administração & dosagem , Administração Oral , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Fitogênicos/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/secundário , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Masculino , Estadiamento de Neoplasias , Taxa de Sobrevida , Resultado do Tratamento , Vimblastina/efeitos adversos , VinorelbinaRESUMO
A randomized, double-blind, placebo-controlled phase III clinical trial was performed to assess megestrol acetate (Megace) as a postsurgical adjuvant therapy for patients with locally advanced malignant melanoma. Patients whose tumors were greater than 1.7 mm thick and had no regional lymph node involvement and patients with regional lymph node involvement were randomized to receive either 160 mg twice per day oral suspension of megestrol acetate or placebo. Treatment was administered for a maximum of 2 years or until disease progression. The study accrued 262 eligible patients. All but two patients were followed until death or a minimum of 4.5 years. Disease progression was documented in 156 patients. Neither progression-free survival (PFS) nor overall survival (OS) was found to differ between the treatments. The median PFS was 2.4 years in the megestrol acetate arm and 2.3 years in the placebo arm. Multivariate analysis revealed a significantly decreased PFS for patients with four or more positive regional lymph nodes and metachronous nodal disease. Median OS was 5.3 years in the megestrol acetate arm and 3.9 years in the placebo arm. Multivariate analysis revealed that OS was significantly decreased for patients 70 years of age or older with four or more positive lymph nodes. Adjuvant therapy with megestrol acetate oral suspension administered at a dose of 160 mg twice a day for 2 years was not found to be effective in prolonging PFS or OS in patients with surgically resected, locally advanced melanoma.
Assuntos
Antineoplásicos/uso terapêutico , Acetato de Megestrol/uso terapêutico , Melanoma/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Método Duplo-Cego , Feminino , Humanos , Metástase Linfática , Masculino , Melanoma/secundário , Melanoma/cirurgia , Pessoa de Meia-Idade , Análise Multivariada , Análise de SobrevidaRESUMO
BACKGROUND: The authors investigated the putative surrogate endpoints of best response, complete response (CR), confirmed response, and progression-free survival (PFS) for associations with overall survival (OS), and as possible surrogate endpoints for OS. METHODS: Individual patient data from 870 untreated extensive stage small-cell lung cancer patients participating in 6 single-arm (274 patients) and 3 randomized trials (596 patients) were pooled. Patient-level associations between putative surrogate endpoints and OS were assessed by Cox models using landmark analyses. Trial-level surrogacy of putative surrogate endpoints were assessed by the association of treatment effects on OS and individual putative surrogate endpoints. Trial-level surrogacy measures included: R(2) from weighted least squares regression model, Spearman correlation coefficient, and R(2) from bivariate survival model (Copula R(2) ). RESULTS: Median OS and PFS were 9.6 (95% confidence interval [CI], 9.1-10.0) and 5.5 (95% CI, 5.2-5.9) months, respectively; best response, CR, and confirmed response rates were 44%, 22%, and 34%, respectively. Patient-level associations showed that PFS status at 4 months was a strong predictor of subsequent survival (hazard ratio [HR], 0.42; 95% CI, 0.35-0.51; concordance index 0.63; P < .01), with 6-month PFS being the strongest (HR, 0.41; 95% CI, 0.35-0.49; concordance index, 0.66, P < .01). At the trial level, PFS showed the highest level of surrogacy for OS (weighted least squares R(2) = 0.79; Copula R(2) = 0.80), explaining 79% of the variance in OS. Tumor response endpoints showed lower surrogacy levels (weighted least squares R(2) ≤0.48). CONCLUSIONS: PFS was strongly associated with OS at both the patient and trial levels. PFS also shows promise as a potential surrogate for OS, but further validation is needed using data from a larger number of randomized phase 3 trials.
Assuntos
Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Biomarcadores Tumorais/análise , Ensaios Clínicos Fase II como Assunto/estatística & dados numéricos , Ensaios Clínicos Fase III como Assunto/estatística & dados numéricos , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Pulmonares/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Carcinoma de Pequenas Células do Pulmão/diagnóstico , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
PURPOSE: Cumulative sensory neurotoxicity (sNT) is the dose-limiting toxicity of oxaliplatin, which commonly leads to early discontinuation of oxaliplatin-based therapy in the palliative and adjuvant settings. In a nonrandomized, retrospective study, intravenous (IV) calcium/magnesium (Ca/Mg) was associated with reduced oxaliplatin-induced sNT. METHODS: Patients with colon cancer undergoing adjuvant therapy with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) were randomly assigned to Ca/Mg (1g calcium gluconate plus 1g magnesium sulfate pre- and post-oxaliplatin) or placebo, in a double-blinded manner. The primary end point was the percentage of patients with grade 2 or greater sNT at any time during or after oxaliplatin-based therapy by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE; version 3) criteria. An oxaliplatin-specific sNT scale and patient questionnaires were also used to assess sNT. After 104 of 300 planned patients were enrolled, the study was closed. This was due to preliminary reports from another trial that suggested that Ca/Mg decreased treatment efficacy; these data were subsequently found to be incorrect. RESULTS: Overall, 102 patients were available for analysis. Ca/Mg decreased the incidence of chronic, cumulative, grade 2 or greater sNT, as measured by NCI CTCAE (P = .038) and also by the oxaliplatin-specific sNT scale (P = .018). In addition, acute muscle spasms associated with oxaliplatin were significantly reduced (P = .01) No effect on acute, cold-induced sNT was found. No substantial differences in adverse effects were noted between Ca/Mg and placebo. CONCLUSION: Despite early termination and decreased statistical power, this study supports IV Ca/Mg as an effective neuroprotectant against oxaliplatin-induced cumulative sNT in adjuvant colon cancer.
Assuntos
Adenocarcinoma/tratamento farmacológico , Antineoplásicos/efeitos adversos , Gluconato de Cálcio/administração & dosagem , Neoplasias do Colo/tratamento farmacológico , Sulfato de Magnésio/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Síndromes Neurotóxicas/prevenção & controle , Compostos Organoplatínicos/efeitos adversos , Transtornos de Sensação/prevenção & controle , Idoso , Quimioterapia Adjuvante , Distribuição de Qui-Quadrado , Método Duplo-Cego , Combinação de Medicamentos , Término Precoce de Ensaios Clínicos , Feminino , Humanos , Infusões Intravenosas , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Síndromes Neurotóxicas/diagnóstico , Síndromes Neurotóxicas/etiologia , Oxaliplatina , Estudos Prospectivos , Transtornos de Sensação/induzido quimicamente , Transtornos de Sensação/diagnóstico , Inquéritos e Questionários , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: The objective of this study was to evaluate the response rate and toxicities of the combination of oral topotecan and carboplatin in patients with untreated extensive stage small cell lung cancer (ES-SCLC). Previous studies have suggested improved outcomes with a topoisomerase I inhibitor in combination with a platinum agent. METHODS: Twenty-six patients with previously untreated, ES-SCLC were evaluable in this phase II trial. All patients received oral topotecan 2.0 mg/m per day on days 1 through 5 and carboplatin at an area under curve of 5 on day 5. Treatment was repeated every 21 days up to a total of 6 cycles. All patients received G-CSF. RESULTS: There were no complete responses and 16 partial responses, for an overall response rate of 62% (95% CI: 41-80). Median time to progression was 6.0 months (95% CI: 4-8), with a median overall survival of 12 months (95% CI: 8-16). This study was closed to accrual early with 26 of a planned 39 patients enrolled because of grade 5 adverse events in 4 (15%) patients (3 neutropenic infections, 1 sudden cardiac death). Eighty-five percent of patients experienced grade 3 or higher hematologic events. The most common severe nonhematologic events included diarrhea, vomiting, dyspnea, hypoxia, and hypotension. CONCLUSIONS: Although this drug regimen has activity as first-line therapy in ES-SCLC, it is associated with excessive hematologic toxicity, which occurred in spite of growth factor support. Despite promising survival estimates, this particular combination and dose level of oral topotecan and carboplatin cannot be recommended.
Assuntos
Carcinoma de Células Pequenas/tratamento farmacológico , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Topotecan/uso terapêutico , Administração Oral , Adulto , Idoso , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Carboplatina/toxicidade , Carcinoma de Células Pequenas/mortalidade , Carcinoma de Células Pequenas/patologia , Progressão da Doença , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Humanos , Injeções Intravenosas , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sobrevida , Fatores de Tempo , Topotecan/administração & dosagem , Topotecan/toxicidade , Resultado do TratamentoRESUMO
PURPOSE: Epidermal growth factor receptor (EGFR) amplification in glioblastoma multiforme (GBM) is a common occurrence and is associated with treatment resistance. Erlotinib, a selective EGFR inhibitor, was combined with temozolomide (TMZ) and radiotherapy (RT) in a phase I/II trial. PATIENTS AND METHODS: Adults not taking enzyme-inducing anticonvulsants after resection or biopsy of GBM were treated with erlotinib (150 mg daily) until progression. Erlotinib was delivered alone for 1 week, then concurrently with TMZ (75 mg mg/m(2) daily) and RT (60 Gy), and finally, concurrently with up to six cycles of adjuvant TMZ (200 mg/m(2) daily for 5 days every 28 days). The primary end point was survival at 1 year. RESULTS: Ninety-seven eligible patients were accrued with a median follow-up time of 22.2 months. By definition, the primary end point was successfully met with a median survival time of 15.3 months. However, there was no sign of benefit in overall survival when comparing N0177 with the RT/TMZ arm of the European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada trial 26981/22981 (recursive partitioning analysis [RPA] class III, 19 v 21 months; RPA class IV, 16 v 16 months; RPA class V, 8 v 10 months, respectively). Presence of diarrhea, rash, and EGFRvIII, p53, phosphatase and tensin homolog (PTEN), combination EGFR and PTEN, and EGFR amplification status were not predictive (P > .05) of survival. CONCLUSION: Although the primary end point was successfully met using nitrosourea-based (pre-TMZ) chemotherapy era historic controls, there was no sign of benefit compared with TMZ era controls. Analyses of molecular subsets did not reveal cohorts of patients sensitive to erlotinib. TMZ chemotherapy combined with RT resulted in improved outcomes compared with historical controls who received nitrosourea-based chemotherapies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dacarbazina/análogos & derivados , Glioblastoma/tratamento farmacológico , Glioblastoma/radioterapia , Quinazolinas/administração & dosagem , Radioterapia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Terapia Combinada/métodos , Dacarbazina/administração & dosagem , Progressão da Doença , Cloridrato de Erlotinib , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Temozolomida , Resultado do TratamentoRESUMO
PURPOSE: To determine the maximum tolerated dose (MTD) and efficacy of pemetrexed and gemcitabine in patients with either biliary tract or gallbladder carcinoma. PATIENTS AND METHODS: Patients with unresectable previously untreated biliary tract cancers were eligible for participation. An initial phase I trial was performed to determine the MTD using an every-2-weeks schedule. The MTD was then used in the phase II portion of the trial. The primary end point for the phase II portion was 6-month survival with a planned accrual of 59 patients. RESULTS: Overall, 63 eligible patients were enrolled. The MTD was established as pemetrexed 500 mg/m2 IV over 10 min and gemcitabine 800 mg/m2 IV at 10 mg/m2 per minute on days 1 and 15 of an every-4-weeks schedule with vitamin B12 and folate supplementation. Fifty-eight patients were included in the phase II portion. Median age was 61 and median follow-up was 18.2 months. A median of three cycles of treatment was given. Six-month survival was 55% and the median survival was 6.6 months (95% confidence interval 5.4-8.7 months) with a median time to progression of 3.8 months (2.4-5.4). Forty-seven (81%) experienced at least one grade 3+ adverse event, and 28 patients (48%) experienced at least one grade 4 adverse event, most of which were due to grade 4 neutropenia. CONCLUSION: The addition of pemetrexed to fixed-dose-rate gemcitabine, in a biweekly schedule, did not enhance the activity of gemcitabine in patients with biliary tract or gallbladder carcinoma.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias da Vesícula Biliar/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Sistema Biliar/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Neoplasias da Vesícula Biliar/patologia , Glutamatos/administração & dosagem , Guanina/administração & dosagem , Guanina/análogos & derivados , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Pemetrexede , Prognóstico , Taxa de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
PURPOSE: Despite the utility of newer antidepressants for alleviating hot flashes, antidepressants do not work adequately enough in many patients. Gabapentin is a nonhormonal agent that also can reduce hot flashes. No data have been available to address whether the combination of both agents would more effectively alleviate hot flashes, compared with gabapentin alone, in patients with inadequate hot flash control with an antidepressant alone. PATIENTS AND METHODS: This was a randomized trial in which 118 patients with inadequate hot flash control on an antidepressant were randomly assigned to receive both an antidepressant and gabapentin versus being weaned off the antidepressant and receiving gabapentin alone. Patients were observed for 5 weeks (including a baseline week in which patients continued on their current antidepressant without gabapentin) during which time they completed validated daily hot flash diaries. RESULTS: Ninety-one patients provided complete data at the 5-week assessment. Regardless of whether or not the antidepressant was continued when gabapentin was started, there was an approximately 50% median reduction in hot flash frequencies (54%; 95% CI, 34% to 70% for combined treatment v 49%; 95% CI, 26% to 58% for gabapentin alone) and scores (56%; 95% CI, 26% to 71% for combined treatment v 60%; 95% CI, 33% to 73% for gabapentin alone). CONCLUSION: Gabapentin seems to decrease hot flashes by approximately 50% in women with inadequate hot flash control who were using an antidepressant. This study saw no significant additional hot flash reduction from continuation of the antidepressant.