RESUMO
We designed a phase I study to determine the maximum tolerated doses of weekly cisplatin and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) (doses escalated alternately) when given concurrently with standard or hyperfractionated radiotherapy (RT) and to define the nature of the dose-limiting toxicity. Chemotherapy-naive patients with locally advanced non-small cell lung cancer received weekly combination cisplatin/paclitaxel with concurrent local RT. Radiation therapy was initially given at the dose of 1.2 Gy twice daily x 5 d/wk x 5 weeks (total dose, 60 Gy). In the last two patient cohorts, the single daily dose was decreased to 2 Gy x 5 d/wk x 6 weeks. Overall, 25 patients were recruited into five different cohorts. Esophagitis was the main nonhematologic toxicity, occurring in 16 of 25 patients (64%; grade 3 or 4 in five). Neutropenia was the most prevalent hematologic toxicity, occurring in 33 of 141 weekly courses, but grade 4 neutropenia was seen in only four courses. Cisplatin/paclitaxel doses of 35 mg/m2/wk and 45 mg/m2/wk, respectively, were safe when standard RT was used, while the cisplatin dose had to be decreased to 30 mg/m2/wk in patients receiving bifractionation. Two complete and 13 partial responses were observed, for a 60% overall response rate (95% confidence interval, 39% to 79%). Median survival was 16 months, with a 66% 1-year actuarial probability. We thus conclude that the cisplatin/paclitaxel combination given weekly can be safely administered concurrent with both standard or hyperfractionated RT. Hyperfractionation is associated with a higher incidence of severe esophagitis and required a slight reduction in cisplatin dose. To verify whether the use of a daily schedule translates into a better therapeutic index, a new phase I study is under way, testing twice-daily cisplatin/paclitaxel concurrently with hyperfractionated RT.
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 , Paclitaxel/administração & dosagem , Adulto , Idoso , Cisplatino/administração & dosagem , Terapia Combinada , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica , Análise de SobrevidaRESUMO
PURPOSE: Both cisplatin (CDDP) and paclitaxel have shown good antitumor activity in non-small-cell lung cancer (NSCLC) patients and are able to potentiate the antitumor effects of radiation therapy (RT). This study aimed to determine the maximum-tolerated doses (MTDs) of CDDP and paclitaxel (escalated alternately) when given concurrently with RT and to define the nature of the dose-limiting toxicity (DLT). PATIENTS AND METHODS: Chemotherapy-naive patients with locally advanced NSCLC received six weekly administrations of a CDDP-paclitaxel combination with concurrent local RT. The starting doses of CDDP and paclitaxel were 30 mg/m2/wk and 35 mg/m2/wk, respectively. RT was initially given at the dose of 1.2 Gy twice daily for 5 days per week for 5 weeks (total dose, 60 Gy) and at a single daily dose of 2 Gy for 5 days per week for 6 weeks in the last two cohorts of patients. The drug doses were escalated alternately until DLT occurred in more than one third of the patients in a given cohort. RESULTS: Overall, 25 patients were recruited through five different cohorts. All were assessable for toxicity. Esophagitis was the main toxicity and occurred in 16 of 25 patients (64%) and was grade 3 or 4 in five of them. At step 3 (CDDP 35 mg/m2/wk and paclitaxel 45 mg/m2/wk), two of five patients had to discontinue treatment because of severe esophagitis and one of these died of complications related to grade 4 esophagitis. However, keeping the same doses of chemotherapy and replacing hyperfractionation with a standard single-day fraction, weekly doses of CDDP and paclitaxel of 35 mg/m2 and 45 mg/m2 could be safely administered. Neutropenia was by far the most relevant hematologic toxicity and occurred in 33 of 141 weekly delivered courses, but it was of grade 4 in only four courses. Substantial pulmonary or neurologic toxicity was not observed in this study. Two complete responses (CRs) and 13 partial responses (PRs) were observed, for a 60% overall response rate (95% confidence interval [CI], 39% to 79%). The median survival time was 16 months, with a 66% 1-year survival probability. CONCLUSION: CDDP 35 mg/m2/wk and paclitaxel 45 mg/m2/wk can be safely administered with concurrent standard RT. The use of hyperfractionation is associated with a more frequent occurrence of severe esophagitis and requires a reduction of the CDDP dose to 30 mg/m2/ wk. Only future randomized trials will elucidate which of these two approaches (standard or hyperfractionated RT) is the better option to improve the outcome of patients with locally advanced 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 , Antineoplásicos Fitogênicos/administração & dosagem , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Esquema de Medicação , Esofagite/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Paclitaxel/administração & dosagem , Dosagem Radioterapêutica , Radioterapia Adjuvante/efeitos adversos , Análise de Sobrevida , Resultado do TratamentoRESUMO
More than 30% of lung cancers arise in patients over 70 years old. Elderly patients are not considered to tolerate chemotherapy, are generally excluded from clinical trials, and are not considered eligible for aggressive cisplatinbased chemotherapy in clinical practice. The aims of the present study were to test the activity and toxicity of a combination of carboplatin and oral etoposide in patients over 70 years old with advanced non small cell lung cancer. Carboplatin was given at a dose of 300 mg/m2, i.v., at day 1, and oral etoposide (50 mg capsules) at a total dose of 100 mg/die from day 1 to day 7, recycled every 4 weeks. Fourteen patients entered the study. Median age was 73 years (range 70-77), 42.9% of patients had at least one concomitant illness. The trial, according to the Gehan design, was terminated earlier because no objective response was observed among the first 14 patients. We reported, according to intent to treat analysis, 2 stable and 12 progressive diseases. Median time to progression was 2 months and median survival 6 months. Remarkable hematological toxicity was recorded. Finally, we do not recommend the combination of carboplatin and oral etoposide, at the doses and schedule used in the present study, in the treatment of elderly patients with advanced NSCLC. The combination might be reconsidered using a different etoposide schedule with chronic administration (21 days).
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Etoposídeo/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Administração Oral , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de Neoplasias , Seleção de Pacientes , Taxa de SobrevidaRESUMO
In order to demonstrate if radiotherapy (RT) is able to reduce the number of local recurrences and to increase the survival rate of patients (pts) with colorectal cancer, the authors are participating in a large randomized international trial with the goal of comparing patients treated with preoperative radiotherapy plus surgery and patients treated only by surgery. The authors noticed that some patients treated with preoperative radiotherapy showed a reduction in tumor size at the time of endorectal ultrasonography. The authors considered the incidence of recurrences in patients responsive to radiotherapy (RT responsive group), in patients non responsive to radiotherapy (RT non responsive group) and in patients not treated with radiotherapy (no RT group) with the aim of establishing if the responsiveness to preoperative radiotherapy could be considered a prognostic factor in colorectal cancer. After a three year follow-up RT responsive group (41 pts) showed no recurrences (0%); RT non responsive group (27 pts) showed 7 (25%) recurrences; no RT group (66 pts) showed 27 (41%) recurrences. Our data indicates that responsiveness to preoperative RT can be considered a prognostic factor. A large number of patients is required to confirm this observation.
Assuntos
Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/radioterapia , Quimioterapia Adjuvante , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Humanos , Estudos Multicêntricos como Assunto , Prognóstico , Radioterapia Adjuvante , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND: Prognosis of unresectable non-small cell lung cancer (NSCLC) patients is disappointing; their median survival time does not exceed 8-12 months. Recently, some authors reported an increased response rate and sometimes a prolonged survival for patients with intrathoracic disease treated with local irradiation combined with cytotoxic drugs. METHODS: Fifty-eight consecutive patients with Stage IIIA or IIIB NSCLC were enrolled in a randomized Phase II trial of alternated treatment composed of four courses of combination chemotherapy and three cycles of local irradiation. Chemotherapy consisted of a randomly selected platinum compound (cisplatin [60 mg/m2] or carboplatin [300 mg/m2]) intravenously (i.v.) on Day 1, epirubicin (50 mg/m2) i.v. on Day 1, and etoposide (100 mg/m2) i.v. on Days 1-3. A course of radiotherapy consisted of 5 consecutive fractions (3 Gy per fraction, 1 fraction per day) for a total dosage of 15 Gy per course. Each course of chemotherapy was alternated every 2 weeks with a course of irradiation so that the entire treatment was performed in 13 weeks. RESULTS: Of the 58 patients, 53 were evaluable for response: 7 showed a complete clinical remission, and 25 reached a partial response, giving an overall response rate of 60% (95% confidence interval, 46%-74%). The tumors of four patients who showed a complete or partial response subsequently were surgically resected, and the complete disappearance of any residual tumor cells was documented histologically in two of them. No difference in response was observed between cisplatin- (16 of 26 [62%]) and carboplatin-treated patients (16 of 27 [59%]), and no correlation was found between response and either stage or histology. Patients enrolled in the carboplatin arm experienced less severe leukopenia and vomiting than did those in the cisplatin arm. Median freedom from progression and overall survival time were 28 and 39 weeks, respectively. Patients who responded had a significantly longer median duration of survival (49 weeks) as compared to non-responders (15 weeks). CONCLUSIONS: The alternated chemoradiotherapy treatment obtained a high response rate with substantial toxicity. This approach did not seem to improve the prognosis of patients significantly. In this setting, the administration of carboplatin instead of cisplatin appeared to be tolerated better by the patients.
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 , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/administração & dosagem , Terapia Combinada , Epirubicina/administração & dosagem , Etoposídeo/administração & dosagem , Estudos de Viabilidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de NeoplasiasRESUMO
The results are presented of ten patients with stage II.B cervical carcinoma, treated with pre-operative after-loading intra-cavitary Iridium 192 followed by radical surgery. The benefits of this combined technique are the reduction of tumor volume, whether in the cervix or in the parametrium. The surgical approach became easier and very few complications were noted. The survival rate after two years follow-up is 100% and no local or distant recurrences have been noted. The following treatment in patients with negative and positive lymph-nodes are discussed.
Assuntos
Braquiterapia , Neoplasias do Colo do Útero/radioterapia , Neoplasias do Colo do Útero/cirurgia , Feminino , Humanos , Histerectomia , Radioisótopos de Irídio/uso terapêutico , Estadiamento de Neoplasias , Dosagem Radioterapêutica , Taxa de Sobrevida , Neoplasias do Colo do Útero/mortalidadeAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Bleomicina/administração & dosagem , Terapia Combinada , Dacarbazina/administração & dosagem , Doxorrubicina/administração & dosagem , Feminino , Seguimentos , Doença de Hodgkin/patologia , Humanos , Masculino , Mecloretamina/administração & dosagem , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Sobreviventes , Fatores de Tempo , Resultado do Tratamento , Vimblastina/administração & dosagem , Vincristina/administração & dosagemRESUMO
26 patients with astrocytoma grade II-III, and 36 with malignant glioma (astrocytoma grade IV or glioblastoma) were submitted three days after surgery to a cycle of combination chemotherapy, including BCNU, VCR, PCZ (BVP). Eighteen days after surgery, patients received 40 Gy (astrocytoma grade II-III) or 45 Gy (malignant glioma) of megavoltage whole-brain irradiation, with an additional boost to the 'tumor' bed of 20 Gy, delivered in 6 weeks. Vincristine was injected weekly during radiotherapy. At the end of radiotherapy, patients received BVP every 6 weeks for at least 8 cycles or until a recurrence or progressive disease. Performance status of grade 1 or 2 was achieved in 15 (60%) and in 5 (20%), respectively, of patients with astrocytoma grade II-III after 6 months, and in 6 ps. (29%) and in 9 ps. (42%) after 12 months of follow-up. Only 2 (5.5%) and 18 (64%) patients with malignant glioma achieved a performance status of grade 1 or 2 after 6 months, and these proportions are 6% and 35%, respectively, after 12 months. After a 5-year follow-up, 59% of patients with astrocytoma are still alive, with a median survival time of 60+ months, whereas only 4% of patients with malignant glioma are alive, with a median of 11.2 months.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/terapia , Astrocitoma/terapia , Neoplasias Encefálicas/radioterapia , Carmustina/administração & dosagem , Terapia Combinada , Glioblastoma/terapia , Glioma/terapia , Humanos , Procarbazina/administração & dosagem , Prognóstico , Dosagem Radioterapêutica , Vincristina/administração & dosagemRESUMO
To assess the prognostic significance of mediastinal involvement of Hodgkin's disease, 91 patients with stage I to III disease treated at our Institute were reclassified according to size of mediastinal disease and other clinical and therapeutic characteristics. Complete remission (CR) was achieved in 46 of 67 (81%) patients without mediastinal involvement, and in 16 of 17 (94%) patients with small mediastinal masses, but only in 10 of 17 (59%) patients with large masses (P less than 0.05). Twenty-seven of 32 (84%) patients treated with irradiation alone and 26 of 28 (93%) patients treated with combined modality therapy reached a CR, whereas such a result was obtained only in 19 of 31 (61%) patients who received MOPP chemotherapy alone (P less than 0.01). In particular, none of the patients with large masses had a CR when treated with chemotherapy alone, whereas no differences in response to therapy were found between patients with large vs. small or no masses when irradiation or combined treatments were utilized. Since combined treatment seems to reach a high proportion of CR and to prevent extranodal relapse, further randomized clinical trials are needed to decide its routine utilization in patients with poor prognostic factors such as large mediastinal adenopathies.
Assuntos
Doença de Hodgkin/patologia , Neoplasias do Mediastino/patologia , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Quimioterapia Combinada , Feminino , Seguimentos , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Humanos , Masculino , Pessoa de Meia-Idade , PrognósticoRESUMO
From January 1978 to December 1980, 42 patients with early stage non-Hodgkin's lymphoma other than of the gastrointestinal tract were treated with radiotherapy and combination chemotherapy. Eighteen patients in stage I were submitted to locally extended-field radiotherapy up to a mean dose of 48 Gy with a Co60 source and, after a 3-week rest period, to 6 cycles of combination chemotherapy. Twenty-four patients in stage II received 3 cycles of combination chemotherapy before and after irradiation, the same as for stage I. Combination chemotherapy consisted of cyclophosphamide, vincristine and prednisone (CVP) for 15 cases with favorable histology (3 NWDL, 1 NPDI, 11 DWDL), whereas it included cyclophosphamide, adriamycin, vincristine and prednisone (CHOP) for 27 cases with unfavorable histology (20 DPDL, 3 DM, 4 DH). Complete remission (CR) was achieved in 35/42 (83%) patients, with a highly significant difference between stage I (100%) and stage II (71%). After 42 months of follow-up, the probability of survival for all patients was 72%. Survival was better for stage I (88%) than for stage II (68%) and for favorable histology (87%) as compared to unfavorable histology (70%). Furthermore, survival was highly influenced by response to therapy. Indeed, actuarial survival rate for CR was 91% as compared to a median survival time of 10.2 months for the remaining patients. Four patients, all with poor histology, relapsed after 5-24 (mean 11) months of CR. Only one of them had an extension in extranodal sites and eventually died, despite the salvage treatment utilized. In our experience, locally extended-field irradiation combined with chemotherapy gave a high proportion of CR and seemed to prevent relapses, particularly in extranodal site.