RESUMO
Hormonal therapy is the preferred systemic treatment for recurrent or metastatic, post-menopausal hormone-receptor-positive breast cancer. Previous studies have shown that there is no cross-resistance between exemestane and reversible aromatase inhibitors. Exposure to hormonal therapy does not hamper later response to chemotherapy. Patients with locally advanced or metastatic, hormonal receptor positive or unknown, breast cancer were treated with oral anastrozole, until disease progression, followed by oral exemestane until new evidence of disease progression. The primary end point of the study was clinical benefit, defined as the sum of complete responses (CR), partial responses (PR) and > 24 weeks stable disease (SD). In all, 100 patients were enrolled in the study. Anastrozole produced eight CR and 19 PR for an overall response rate of 27% (95% CI: 18.6-36.8%). An additional 46 patients had long-term (> 24 weeks) SD for an overall clinical benefit of 73% (95% CI: 63.2-81.4). Median time to progression (TTP) was 11 months (95% CI: 10-12). A total of 50 patients were evaluated for the second-line treatment: exemestane produced one CR and three PR; 25 patients had SD which lasted > or = 6 months in 18 patients. Median TTP was 5 months. Toxicity of treatment was low. Our study confirms that treatment with sequential hormonal agents can extend the period of time during which endocrine therapy can be used, thereby deferring the decision to use chemotherapy.
Assuntos
Androstadienos/uso terapêutico , Antineoplásicos Hormonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Nitrilas/uso terapêutico , Triazóis/uso terapêutico , Administração Oral , Adulto , Idoso , Anastrozol , Androstadienos/administração & dosagem , Antineoplásicos Hormonais/administração & dosagem , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Nitrilas/administração & dosagem , Triazóis/administração & dosagemRESUMO
AIM: To verify the rationale of a pelvic stop-flow technique for the perfusion of high-doses of mitomycin C and anthacyclines in patients with inoperable, recurrent pelvic cancer. METHODS: The stop-flow technique was realized by using percutaneous double-balloon arterial-venous catheters that selectively isolate the pelvic vascular section and a perfusion provided by an extracorporeal pump for 20 min. Ten patients (pts) with unresectable pelvic recurrence from colon-rectal cancer were treated with a combination of Mitomycin C (MMC, 20 mg/sqm) plus doxorubicin (DOXO, 75 mg/sqm; 8pts) or epirubicin (EPI, 75 mg/sqm; 2pts) infused into the isolated pelvic compartment. Blood samples were collected from the extracorporeal vascular flow and from peripheral plasma, and analysed for drug quantitation. RESULTS: During the procedure, there were no technical or hemodynamic complications, and no deaths occurred during surgery or in the postoperative period. MMC and DOXO peak levels measured in the extracorporeal system which irrotates the tumor area, were on average 21.6 (range: 4.3-44.3, MMC) and 17.2 (range: 1.8-48.4, DOXO) times higher than those observed in the peripheral blood. Similarly; the area under concentration (AUC) versus time curves measured in the pelvic compartment during stop-flow perfusion were 19.9 (range: 3.8-45.0, MMC) and 13.4 (range: 1.2-26.6, DOXO) times higher than the corresponding value in peripheral circulation. The drug percentage eliminated in the ultra filtrate was only 7.7% (MMC) and 0.9% (DOXO), and the plasmatic AUC(0-24) were similar to those observed with iv bolus of equivalent drug doses. Minimal systemic and local toxicities were observed. One complete pathological and 2 partial responses were observed; pain remission in 8/10 patients. median survival was 12 months (8-31). CONCLUSION: The endo-arterial administration into the local vasculature produces high pelvic-systemic concentration gradients during the stop-flow perfusion with limited local and systemic toxicity. The encouraging clinical results suggest further evaluation.
Assuntos
Antraciclinas/administração & dosagem , Antibióticos Antineoplásicos/administração & dosagem , Quimioterapia do Câncer por Perfusão Regional , Neoplasias Colorretais/tratamento farmacológico , Mitomicina/administração & dosagem , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Pélvicas/tratamento farmacológico , Adolescente , Adulto , Idoso , Neoplasias Colorretais/patologia , Doxorrubicina/administração & dosagem , Epirubicina/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Pélvicas/secundário , Resultado do TratamentoRESUMO
UNLABELLED: A phase II trial was undertaken to test the activity and toxicity of carboplatin (300 mg/m2, i.v. day 1) + epirubicin (75 mg/m2, i.v. day 1) + VP-16 (100 mg/m2, i.v. days 1 to 3) + lenograstim (5 mcg/kg, s.c. days 6 to 15) administered every 3 weeks for 4 cycles and subsequent chest irradiation (50 Gy) + daily carboplatin (25 mg/m2) in the first-line treatment of adults affected by limited small cell lung cancer (SCLC). PATIENTS AND METHODS: A single-stage phase II design was used; the complete response (CR) rate after chest radiotherapy was the primary end-point. Twenty-three CRs were required out of 38 patients to consider the treatment worthy of further study. Prophylactic cranial irradiation (PCI) was planned in case of CR. Patients aged < or = 70 were eligible if they had limited SCLC, a performance status not worse than 2 by the ECOG scale and no prior chemotherapy or radiotherapy. RESULTS: From January 1995 to April 1999, 33 patients were enrolled; the median age was 60 years. All the patients started chemotherapy; 23 patients received chest irradiation and concurrent daily carboplatin; 11 patients also received PCI. Toxicity was generally mild. Sixteen CRs (48.5%, 95% CI: 30.8-66.5) were recorded; the objective response rate was 72.7% (95% CI: 54.5-86.7). The median time-to-progression was 7.9 months (95% CI: 6.5-10.4). The median-survival was 10.7 months (95% CI: 9.2-16.1). CONCLUSION: Induction chemotherapy with carboplatin + epirubicin + VP-16 followed by chest irradiation plus concurrent daily carboplatin is well-tolerated but not sufficiently active to warrant further study in the treatment of patients with limited SCLC.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Terapia Combinada , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Lenograstim , Masculino , Pessoa de Meia-Idade , Radiossensibilizantes/administração & dosagem , Radiossensibilizantes/efeitos adversos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversosRESUMO
Primary cutaneous plasmacytomas of the chest wall are very rare. In this report we describe a case of a 70-years old man, affected by chronic obstructive pulmonary disease and renal failure. He was admitted because of a painful tumor on the right lateral chest wall: a transcutaneous fine needle aspiration and excisional biopsy revealed as a metastasis from lung cancer without clinical and or radiological evidence of pulmonary tumors and or other neoplasms. Because of failure of chemotherapy, the patient had undergone to bone marrow biopsy that it revealed medullary plasmacytosis < 5% plasma cells with a beta 2 microglobulin elevated. An other following excisional biopsy of a chest wall with immunocytochemistry revealed to be a cutaneous plasmacytomas. The patient was treated with local irradiation for a total dose of 40 cGy and systemic chemotherapy, stopped because of death by myocardial infarction. Cutaneous plasmacytomas appear to be more aggressive than non cutaneous extramedullary plasmacytomas; they should be separately categorized from them in future studies.
Assuntos
Plasmocitoma/patologia , Neoplasias Cutâneas/patologia , Idoso , Humanos , Masculino , TóraxRESUMO
Gemcitabine and paclitaxel (PTX) are among the most active new drugs in advanced breast and ovarian cancer. In this Phase I study, we used fixed doses of gemcitabine administered on days 1 and 8 and escalating doses of paclitaxel on day 1 of a 21-day cycle in patients with pretreated metastatic breast or ovarian cancer. The dose of gemcitabine was fixed at 1,000 mg/m2; PTX was commenced in the first small patient group at a dose of 90 mg/m2, which was then escalated in subsequent groups by 30 mg/m2 per step. From the third dose level onwards, all patients received granulocyte colony-stimulating factor 300 microg by subcutaneous injection on days 5 and 6, and granulocyte macrophage colony-stimulating factor on days 15-18. Cohorts of at least 3 patients were treated at each dose level. Dose escalation was stopped if at least a third of the patients in a given cohort had dose-limiting toxicity (DLT), which was defined as grade 4 neutropenia or thrombocytopenia, or grade 3-4 non-haematological toxicity. The maximum tolerated dose (MTD) was defined as the dose level immediately below that causing DLT in one-third of the patients or more. Evaluation of the tumour response was performed every three cycles. Forty-five patients (31 with breast cancer, 14 with ovarian cancer) were treated at seven different dose levels. Only at the seventh PTX dose level was DLT observed after the first course of therapy: three grade 4 neutropenia, one grade 4 thrombocytopenia, and one grade 4 anaemia. DLT occurred in 5/6 patients at at PTX dose of 270 mg/m2; therefore dose escalation was stopped at that level and the dose immediately before it (PTX 240 mg/m2) was considered as the MTD and recommended for further studies. No toxic deaths occurred. Grade 3-4 uncomplicated neutropenia was observed in four patients. Three had uncomplicated grade 3-4 thrombocytopenia. One patient had grade 3 and one grade 4 anaemia. Nonhaematological side effects were generally mild. Among 30 evaluable patients with metastatic breast cancer, four complete responses (CR) (13%) and 12 partial responses (PR) (40%) were observed, for an overall response rate of 53% (95% confidence interval (CI) 34-72). The median duration of response was 31 weeks. Among 13 evaluable patients with advanced ovarian cancer, one CR (8%) and five PRs (38%) were observed, for an overall response rate of 46% (95% CI 19-78). The median duration of response was 32 weeks. Our study shows that gemcitabine and PTX can be administered in combination in patients with breast and ovarian cancer without unexpected toxicities and with encouraging therapeutic results.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adulto , Idoso , Neoplasias da Mama/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Neoplasias Ovarianas/patologia , Paclitaxel/administração & dosagem , Trombocitopenia/induzido quimicamente , GencitabinaRESUMO
Gemcitabine and paclitaxel are among the most active new agents in non-small cell lung cancer (NSCLC) and are worth considering for second-line chemotherapy. In this phase I-II study, we combined gemcitabine and paclitaxel for second-line treatment of advanced NSCLC. Gemcitabine doses were kept fixed at 1000 mg/m2 on day 1 and 8, and paclitaxel doses were escalated from 90 mg/m2 on day 1 of the 21-day cycle. Thirty-seven patients were treated at six different dose levels. Grade 4 neutropenia was dose-limiting toxicity (DLT), since it occurred in two out of six patients treated at paclitaxel 240 mg/m2; the paclitaxel dose level just below (210 mg/m2) was selected for phase Il evaluation. Non-hematologic toxicity was mild. One complete response (CR) (3%) and 13 partial responses (PR) (36%) were observed in 36 evaluable patients for an overall response rate of 39% (95% C.I., 23-57%). Median duration of response was 35 weeks (range, 8-102). All of the observed objective responses occurred in the 19 patients who had previously responded to the first-line therapy. Median survival was 40 weeks (range, 8-108 weeks). The combination of gemcitabine and paclitaxel is a feasible, well-tolerated, and active scheme for second-line treatment of advanced NSCLC; further evaluation, at least in selected patients, such as those previously responding to first-line chemotherapy, is definitely 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/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Relação Dose-Resposta a Droga , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Análise de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
PURPOSE: Platinum-based chemotherapy currently represents standard treatment for advanced non-small-cell lung cancer. Gemcitabine is one of the most interesting agents currently in use in advanced non-small-cell lung cancer, and high response rates have been reported when it is administered in combination with cisplatin. The aim of the present study was to evaluate the combination of gemcitabine and carboplatin in a phase I-II study. PATIENTS AND METHODS: Chemotherapy-naive patients with stage IIIB-IV non-small-cell lung cancer received carboplatin at area under the concentration-time curve (AUC) 5 mg/mL/min and gemcitabine at an initial dose of 800 mg/m2, subsequently escalated by 100 mg/m2 per step. Gemcitabine was administered on days 1 and 8 and carboplatin on day 8 of the 28-day cycle. Dose escalation proceeded up to dose-limiting toxicity (DLT), which was defined as grade 4 neutropenia or thrombocytopenia or grade 3 nonhematologic toxicity. RESULTS: Neutropenia was DLT, inasmuch as it occurred in three of five patients receiving gemcitabine 1,200 mg/m2. Nonhematologic toxicities were mild. Gemcitabine 1,100 mg/m2 plus carboplatin AUC 5 was recommended for phase II studies. An objective response was observed in 13 (50%) of 26 patients, including four complete responses (15%) and nine partial responses (35%). Median duration of response was 13 months (range, 3 to 23 months). Median overall survival was 16 months (range, 3 to 26 months). CONCLUSION: The combination of gemcitabine and carboplatin is well tolerated and active. Neutropenia was DLT. The observed activity matches that observable in cisplatin-gemcitabine studies, whereas duration of response and survival are even higher. A phase II trial is under way.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Alopecia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Esquema de Medicação , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Estadiamento de Neoplasias , Neutropenia/induzido quimicamente , Indução de Remissão , Trombocitopenia/induzido quimicamente , GencitabinaRESUMO
Paclitaxel and vinorelbine are among the most active new agents in metastatic breast cancer. Both in vitro and in vivo studies have shown that the combined administration of these two microtubule-targeting agents is feasible and worthwhile. Based on the promising preclinical data, patients with metastatic breast cancer no longer amenable to conventional treatment were entered into a phase I/II study in which the vinorelbine dose was fixed at 30 mg/sqm and paclitaxel was started at 90 mg/sqm and then subsequently escalated by 30 mg/sqm per step. Cycles were repeated every 21 days. Hematopoietic growth factor support was provided from the 4th dose level onwards. Grade III neutropenia was observed only in 2 patients treated at the 5th dose level. Thrombocytopenia never reached grade 3. Neurotoxicity was considered dose-limiting, since grade 3 peripheral neuropathy occurred in all three patients treated at the 6th dose level. Other toxicities were mild. Paclitaxel 210 mg/sqm and vinorelbine 30 mg/sqm was the selected combination for phase II. Overall response rate in 34 evaluable patients was 38% (95% confidence interval (C.I.), 22% to 54%). In particular, 3 complete responses (9%) and 10 partial responses (29%) were observed. The observed level of antitumor activity, with an overall response rate of 38% and a median duration of response of 12 months, is of interest, since the study was targeted only to anthracycline-pretreated patients, most of whom had adverse prognostic features. The evaluation of a combination of vinorelbine and paclitaxel as first-line therapy in metastatic breast cancer seems worthwhile and is currently undergoing.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Paclitaxel/uso terapêutico , Vimblastina/análogos & derivados , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Paclitaxel/efeitos adversos , Vimblastina/efeitos adversos , Vimblastina/uso terapêutico , VinorelbinaRESUMO
BACKGROUND: Vinorelbine and paclitaxel interfere with mitotic spindle function through different mechanisms of action. Both of the drugs show antitumor activity in small-cell lung cancer when used as single agents; furthermore, in vitro and in vivo studies have shown a synergistic activity between the two drugs. PATIENTS AND METHODS: Patients with small-cell lung cancer no longer amenable to conventional treatment were entered into a phase I study in which vinorelbine was given at a fixed dose of 30 mg/m2 by 15-min intravenous infusion, whereas paclitaxel was given by 3-h infusion starting 1 h after vinorelbine at an initial dose of 90 mg/m2, which was subsequently escalated by 30-mg/m2 steps. Cycles were repeated every 21 days. RESULTS: Grade 3 neutropenia was observed only in three patients treated at the fifty dose level. Thrombocytopenia never reached grade 3. Neurotoxicity was considered dose-limiting, since grade 3 peripheral neuropathy occurred in three of five patients treated at the fifth dose level (paclitaxel 210 mg/m2). Other side effects were generally mild. The overall response rate in 22 evaluable patients was 32% (95% CI 13-51%); in particular, 1 complete response (4.5%) and 6 partial responses (27.3%) were observed. The maximally tolerated doses recommended for phase II studies are 180 mg/m2 for paclitaxel and 30 mg/m2 for vinorelbine. The observed myelosuppression was less severe than anticipated on the basis of the effects of each drug alone. CONCLUSIONS: The promising activity of this drug combination warrants a phase II study in untreated patients with extensive-stage small-cell lung cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Sistema Nervoso/efeitos dos fármacos , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Trombocitopenia/induzido quimicamente , Vimblastina/administração & dosagem , Vimblastina/efeitos adversosRESUMO
43 patients with stage III NSCLC (non-small cell lung cancer) entered a phase II study aimed at evaluating the toxicity and the activity of a combined modality programme including an accelerated split-course schedule (type B) of thoracic radiation therapy and a combination chemotherapy with vinorelbine and carboplatin. An objective response was achieved in 18/42 evaluable patients (5 complete and 13 partial responses), for an overall response rate of 43% (95% confidence interval, 28-58%). Four complete responses had a duration which exceeded 16 months. Treatment was well tolerated; grade III myelotoxicity occurred in only 14% of patients and treatment was delayed in only 2 cases because of grade 3 oesophagitis. Both tolerability and efficacy data suggest that this regimen holds promise for the treatment of patients with stage III NSCLC.
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 , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/patologia , Terapia Combinada , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia/efeitos adversos , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/análogos & derivados , VinorelbinaRESUMO
Low-grade non-Hodgkin's lymphoma and multiple myeloma are chemosensitive malignancies, but are rarely curable because of primary or acquired drug resistance. Interferon has been shown to modulate the multidrug resistance phenotype and to reinduce chemosensitivity in patients with chemoresistant tumors. Fifteen patients with multiple myeloma and 64 patients with low/intermediate grade non-Hodgkin's lymphoma unresponsive to initial chemotherapy were treated with alpha 2b interferon for 2 months. In case of an objective response, treatment was continued until disease progression; non-responding patients received the same chemotherapy to which they were resistant, preceded by a 5 day course of interferon. Interferon salvage monotherapy induced an objective response in 1/15 patients with multiple myeloma and in 7/64 patients with non-Hodgkin's lymphoma. An objective response was achieved after retreatment with first-line chemotherapy preceded by interferon in 4/14 patients (28.6%) with multiple myeloma and in 20/56 evaluable patients (35.7%) with non-Hodgkin's lymphoma. Toxicity was moderate, predictable, manageable, and never caused interruption of the treatment. Interferon appears to be able to modulate chemosensitivity of tumors refractory to chemotherapy with several potential mechanisms, including an effect on drug accumulation; its utilization in this setting warrants further evaluation.
Assuntos
Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Interferon-alfa/uso terapêutico , Linfoma não Hodgkin/terapia , Mieloma Múltiplo/terapia , Adulto , Idoso , Antineoplásicos/efeitos adversos , Resistencia a Medicamentos Antineoplásicos/fisiologia , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Masculino , Pessoa de Meia-Idade , Proteínas RecombinantesRESUMO
Forty-one patients with advanced breast cancer were given carboplatin and vinorelbine as second-line therapy. Overall objective response rate was 46% (95% confidence interval 26-56%). Myelotoxicity was the most frequently observed toxic effect; grade III-IV leucopenia occurred in 46% of the patients. Our regimen is active as second-line chemotherapy for advanced breast cancer and warrants further evaluation.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Leucopenia/induzido quimicamente , Metástase Neoplásica , Flebite/induzido quimicamente , Indução de Remissão , Terapia de Salvação , Resultado do Tratamento , Vimblastina/administração & dosagem , Vimblastina/efeitos adversos , Vimblastina/análogos & derivados , VinorelbinaRESUMO
44 patients with advanced breast cancer were treated with high-dose epirubicin (130 mg/sqm), because of its steep dose-response curve. Lonidamine and alpha interferon were administered as well with the aim of increasing epirubicin uptake and overcoming drug resistance. Granulocyte-colony stimulating factor support was provided. 14 complete responses and 22 partial responses were observed in 40 evaluable patients for a 90% overall response rate. Median duration of response was 12 months for complete responders, 7 months for partial responders. In two cases the complete response has lasted for more than two years. Myelosuppression, infection, and cardiac toxicity were the main treatment-related toxic effects. These results are encouraging enough to justify a randomized comparison of our chemotherapy program with standard regimens used in advanced breast cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/terapia , Epirubicina/toxicidade , Indazóis/toxicidade , Interferon-alfa/toxicidade , Interferon-alfa/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/toxicidade , Biomarcadores Tumorais/sangue , Neoplasias da Mama/patologia , Epirubicina/administração & dosagem , Feminino , Seguimentos , Fator Estimulador de Colônias de Granulócitos e Macrófagos/uso terapêutico , Humanos , Indazóis/administração & dosagem , Interferon alfa-2 , Menopausa , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Pós-Menopausa , Pré-Menopausa , Proteínas RecombinantesRESUMO
Forty-five patients with stage III-IV low grade non-Hodgkin's lymphoma (NHL) were treated with a non-intensive polychemotherapy regimen including chlorambucil-vincristine and cytarabine (Ara-C), termed COA, for a total of 366 courses, beginning in June 1986. Grade 4 myelotoxicity occurred in only 4/45 patients. No treatment related death was observed. All patients were evaluable for response. Overall, 38 (84%) objective responses, including 31 (69%) complete responses (CR), were observed. At a median follow-up of 57 (21-84+) months, only 8 deaths occurred. Twenty-seven (60%) patients are still disease-free. All disease-free patients were in their first CR. The seven-year estimated survival is 71% and the estimated 7-year progression-free survival (PFS) was 48%. The estimated probability of complete responders to be disease-free at 6 years is 78%. Pretreatment laboratory parameters (serum levels of thymidine kinase, LDH and TNF-alpha showed a good prognostic relevance at using univariate analysis. At multivariate analysis, only the pretreatment serum levels of TNF-alpha were significantly associated with a higher CR achievement probability (p = 0.02) and a longer PFS (p = 0.02). We established a risk model for clinical outcome based on these 3 parameters. Patients having all parameters within the normal range at diagnosis, showed a very good prognosis (100% 7-year PFS and survival), while patients with all parameters increased had a very poor prognosis (0% 7-year PFS and 22% 7-year survival). In conclusion, COA treatment appears to be a non-toxic and very effective treatment for low-grade non-Hodgkin's lymphomas.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Adulto , Idoso , Biomarcadores Tumorais/sangue , Clorambucila/administração & dosagem , Citarabina/administração & dosagem , Estudos de Avaliação como Assunto , Feminino , Humanos , Linfoma não Hodgkin/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Qualidade de Vida , Timidina Quinase/sangue , Fator de Necrose Tumoral alfa/metabolismo , Vincristina/administração & dosagemRESUMO
43 patients with metastatic colorectal Cancer pretreated with 5-fluorouracil-based chemotherapy received vinorelbine plus 5-fluorouracil plus folinic acid with the aim of evaluating vinorelbine activity in advanced colorectal cancer and its potential synergism with commonly used drugs. 9 partial responses were observed, for an;overall objective response rate of 20.9%. 20 additional patients had stable disease (46.5%). Median duration of response was 7 months. Median survival from the start of treatment was 6 months. The main toxic effect was myelosuppression. We conclude that our regimen is active enough to warrant further evaluation in advanced colorectal cancer.
RESUMO
Twenty-two patients with locally advanced inoperable gastric cancer received neoadjuvant chemotherapy with a modified 5-fluorouracil, doxorubicin, methotrexate (FAMTX) regimen. The patients who achieved at least a stable disease were considered eligible for surgery with curative intent, which was performed in 19 cases. 16 patients (all responsive to neoadjuvant chemotherapy) were rendered disease-free by the combined approach. No treatment-related deaths occurred; grade III leukopenia was observed in only 3 cases. The preliminary results of this study indicate the feasibility of our treatment approach; randomized trials are awaited to properly evaluate the role of neoadjuvant chemotherapy in locally advanced gastric cancer.
RESUMO
21 untreated ovarian cancer patients with stage III and minimal tumour size, were given weekly intraperitoneal (i.p.) carboplatin (150 mg/m2) and alpha-2b interferon (IFN) (30 million U/m2) for a total of 12 courses, from June 1989 to February 1993. To date, a total of 248 courses have been administered. Toxicity was seldom severe, although fever (179 courses), fatigue (141 courses) and other IFN-related side-effects were very frequent. No patient refused to continue treatment, but in 5 patients IFN dose had to be reduced, and in 1 it was discontinued. The IFN mean delivered dose intensity was 19.8 million U/m2 week. Grade 3-4 myelotoxicity occurred in 7 patients (39 courses), but no deaths related to treatment occurred. The actual mean dose intensity of carboplatin was 121.5 mg/m2 week. To date, 20 patients have completed treatment and are evaluable for response. Of 11 patients with tumour size < or = 5 mm, 10 (91%) achieved a pathological complete response (pCR) as did 4/9 (44%) of those with tumour > 5 mm at entry, for a 70% (95% confidence interval 50-90) overall pCR rate. At a median follow-up of 21 months (range 4-46), only one death occurred. The probability of being alive at almost 4 years was 91% in the entire group (100% in those with tumour size less than 5 mm). Only 1 of 14 patients who achieved a pCR relapsed. This i.p. combination seems a feasible approach to previously untreated ovarian cancer patients with minimal tumour burden. IFN dosage should be reduced to improve tolerance. In view of the very high pCR rate achieved in the group of patients with smaller tumours, a randomised trial is warranted to compare this approach to standard treatment in these patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Interferon-alfa/administração & dosagem , Neoplasias Ovarianas/terapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Interferon alfa-2 , Interferon-alfa/efeitos adversos , Pessoa de Meia-Idade , Neoplasia Residual , Neoplasias Ovarianas/mortalidade , Projetos Piloto , Proteínas RecombinantesRESUMO
Hyperfractionated split course radiotherapy combined with carboplatin, etoposide and mitomycin C was administered to 76 patients with stage III non-small cell lung cancer. Grade 4 leukopenia occurred in 5 patients; 4 toxic deaths were observed. The overall response rate was 45%, including a 9% rate of complete responses, which lasted > 12 months in four cases. The median survival was 13 months, 2-year progression-free survival 17%, actuarial 2-year survival rate 22%. Age > 65, performance status > 1, no response to prior treatment were predictors of poor outcome. Our treatment plan, particularly because of the long lasting complete responses, warrants further investigation.
RESUMO
Eighteen patients with advanced ovarian cancer not or no longer responding to cisplatinum and epidoxorubicin including combination chemotherapy were retreated with the above two drugs in combination with lonidamine and interferon, administered with the aim of restoring chemosensitivity. Overall response rate was 32%, with one durable complete response and four partial responses. Toxicity was quite manageable, myalgia being the main additional toxic effect with respect to those reported with conventional chemotherapy. Our study emphasizes the need for additional trials with agents able to overcome drug resistance, which is the chief determinant of treatment failure in advanced ovarian cancer.
RESUMO
Twenty-six patients with locally advanced, inoperable gastric cancer were treated with carboplatin, epidoxorubicin, 5-fluorouracil (FEP) plus alpha 2b interferon. Total gastrectomy was performed in patients achieving clinical complete or partial response. The overall response rate after neoadjuvant chemotherapy was 67%. In 13/15 patients undergoing surgery no residual tumor was evident after resection. After a median follow-up of 14 months, 4/13 disease-free patients have relapsed. The median survival time is 13 months for all patients, and 19 months for disease-free patients; in four patients survival time exceeds twenty-four months. Our multimodality program is effective in locally advanced gastric cancer and warrants further evaluation.