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Intensive induction treatment of small cell bronchogenic carcinoma with cyclophosphamide, methotrexate, and etoposide
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two did not received the drug. There were no complete or partial remissions in this study. Three patients had disease stabilization for a median of i0 weeks (range 6-17). Toxicity was mainly hematologic. Nausea and vomiting were moderate. ACLA-A in the dose schedules used, appears to have no activity in large cell and adenocarcinoma of the lung. High-dose Cyclophosphamide in Small-Cell Carcinoma of the Lung. Souhami, R.L., Finn, G., Gregory, W.M. et al. Department of Radiotherapy and Oncology, University College Hospital, London WCI, U . K . J . Clin. Oncol. 3: 958963, 1985. Eighteen patients with untreated smallcell cancer of the lung have been treated with cyclophosphamide 200 mg/kg on two occasions at an interval of 4 weeks. An additional 8 patients received etoposide in addition to cyclophosphamide. Measurements of tumor volume were made by thoracic computed tomographic (CT) scan before and after each cycle. When compared with out previous study in which only one cycle of cyclophosphamide was given, the double procedure did not increase response rate, decrease the incidence of local relapse, or prolong the relapse-free interval. Survival after relapse was shorter with two cycles of chemotherapy mainly due to greater difficulty in administering further chemotherapy. The CT scans showed a decrease in tumor colume from 99.2 cc to 21 cc after the first cycle, but a smaller decrease to 14.1 cc after the second. These results show that the rapid emergence of drug resistance imposes limitations on the use of very high-dose cytotoxic chemotherapy. High-Dose Cyclophosphamide and VP 16 as Late Dosage Intensification Therapy for Small Cell Carcinoma of Lung. Cunningham, D., Banham, S.W., Hutcheon, A.H. et al. Department of Respiratory Medicine, Glasgow Royal Infirmary, Glasgow, U.K. Cancer Chemother. Pharmacol. 15: 303-306, 1985. This study investigated the use of late dose intensification therapy (LDIT) with cyclophosphamide (180 mg/kg) and VP 16 (i g/m ~) plus autologous bone marrow rescue in 22 patients with small cell lung cancer (SCLC). These patients were selected from a group of 95 patients who received three courses of a fivedrug induction regimen comprising cyclophospham~de (750-1000 mg/m ~, adriamycin (40 mg/m ), VP 16 (109 mg/m-) for 3 days, methotrexate (50 mg/m ) and vincristine (2 mg) (CAVMO). There were 16 p a tients with limited disease,
8 of whom were in complete remission (CR) and 8 in partial remission (PR) after the induction therapy. The other 6 patients had extensive disease; 3 of these achieved CR and 3 PR after induction therapy. Of the ii patients in PR, 5 responded to LDIT; 3 had a further PR, and 2 CR. Subsequent to LDIT radiotherapy 4000 cGY was given to the primary site in i0 of the 22 patients. Since the start of the study, 19 of the 22 patients have relapsed and died (median survival ii months), while 3 remain alive and in remission at ii, ii, and 24 months. Comparison of the survival of patients receiving LDIT with that of an equivalent group (with respect to staging and response to induction chemotherapy) of patients who received induction chemotherapy alone showed no significant difference. In this study, LDIT following conventional induction therapy in patients with chemosensitive tumours did not improve survival. Intensive Induction Treatment of Small Cell Bronchogenic Carcinoma w i t h C y c l o p h o s p h a m i d e , Methotrexate, and Etoposide. Bonomi, P., O-Reilly, W., Vogl, S.E. et al. Section of Medical Oncology, Department of Internal Medicine, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, U.S.A. Cancer Treat. Rep. 69: 10071009, 1985. Fifty-six patients with histologically confirmed small cell bronchogenic carcinoma were treated with cyclophosphamide, methotrexate, and etoposide. While methotrexate doses were modified for mucositis during the 6-week induction period, none of the drug doses were modified for hematologic toxicity. The overall response rate was 66%, with 16% complete remissions; median survival duration was 28 weeks. In %2 patients, the leukocyte count fe~l below 1000/mm-, and there were four deaths in febrile, leukopenic pa£ients. Diffuse pulmonary infiltrates were observed in eight patients, and three died from respiratory insufficiency. Lung biopsy in two patients and autopsy in two additional patients showed interstitial changes consistent with drug injury. This regimen produced considerable hematologic and apparent pulmonary toxicity while offering no advantages in response rate or survival duration. Intensive Induction Chemotherapy for Small Cell Anaplastic Carcinoma of the Lung. O'Donnell, M.R., Ruckdeschel, J.C., Baxter, D. et al. Division of Oncology, Albany Medical College, Albany, NY 12208, U.S.A. Cancer Treat. Rep. 69: 571-575, 1985. The role of intensive induction chemotherapy in small cell cancer of the lung remains unclear. Twenty-eight newly diagnosed patients with small cell lung cancer were randomized to receive either high-dose or standard-dose cyclophosphamide, vincristine, and semustine in a trial where the dose of induction chemotherapy was the sole treatment variable. Complete responses (CR) were achieved in 57% of patients receiving high-dose therapy as compared to 21% of patients receiving standard-dose therapy (P < 0.05). There was a higher rate of severe toxicity in the high-dose group (P < 0.01). The over-
two did not received the drug. There were no complete or partial remissions in this study. Three patients had disease stabilization for a median of i0 weeks (range 6-17). Toxicity was mainly hematologic. Nausea and vomiting were moderate. ACLA-A in the dose schedules used, appears to have no activity in large cell and adenocarcinoma of the lung. High-dose Cyclophosphamide in Small-Cell Carcinoma of the Lung. Souhami, R.L., Finn, G., Gregory, W.M. et al. Department of Radiotherapy and Oncology, University College Hospital, London WCI, U . K . J . Clin. Oncol. 3: 958963, 1985. Eighteen patients with untreated smallcell cancer of the lung have been treated with cyclophosphamide 200 mg/kg on two occasions at an interval of 4 weeks. An additional 8 patients received etoposide in addition to cyclophosphamide. Measurements of tumor volume were made by thoracic computed tomographic (CT) scan before and after each cycle. When compared with out previous study in which only one cycle of cyclophosphamide was given, the double procedure did not increase response rate, decrease the incidence of local relapse, or prolong the relapse-free interval. Survival after relapse was shorter with two cycles of chemotherapy mainly due to greater difficulty in administering further chemotherapy. The CT scans showed a decrease in tumor colume from 99.2 cc to 21 cc after the first cycle, but a smaller decrease to 14.1 cc after the second. These results show that the rapid emergence of drug resistance imposes limitations on the use of very high-dose cytotoxic chemotherapy. High-Dose Cyclophosphamide and VP 16 as Late Dosage Intensification Therapy for Small Cell Carcinoma of Lung. Cunningham, D., Banham, S.W., Hutcheon, A.H. et al. Department of Respiratory Medicine, Glasgow Royal Infirmary, Glasgow, U.K. Cancer Chemother. Pharmacol. 15: 303-306, 1985. This study investigated the use of late dose intensification therapy (LDIT) with cyclophosphamide (180 mg/kg) and VP 16 (i g/m ~) plus autologous bone marrow rescue in 22 patients with small cell lung cancer (SCLC). These patients were selected from a group of 95 patients who received three courses of a fivedrug induction regimen comprising cyclophospham~de (750-1000 mg/m ~, adriamycin (40 mg/m ), VP 16 (109 mg/m-) for 3 days, methotrexate (50 mg/m ) and vincristine (2 mg) (CAVMO). There were 16 p a tients with limited disease,
8 of whom were in complete remission (CR) and 8 in partial remission (PR) after the induction therapy. The other 6 patients had extensive disease; 3 of these achieved CR and 3 PR after induction therapy. Of the ii patients in PR, 5 responded to LDIT; 3 had a further PR, and 2 CR. Subsequent to LDIT radiotherapy 4000 cGY was given to the primary site in i0 of the 22 patients. Since the start of the study, 19 of the 22 patients have relapsed and died (median survival ii months), while 3 remain alive and in remission at ii, ii, and 24 months. Comparison of the survival of patients receiving LDIT with that of an equivalent group (with respect to staging and response to induction chemotherapy) of patients who received induction chemotherapy alone showed no significant difference. In this study, LDIT following conventional induction therapy in patients with chemosensitive tumours did not improve survival. Intensive Induction Treatment of Small Cell Bronchogenic Carcinoma w i t h C y c l o p h o s p h a m i d e , Methotrexate, and Etoposide. Bonomi, P., O-Reilly, W., Vogl, S.E. et al. Section of Medical Oncology, Department of Internal Medicine, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612, U.S.A. Cancer Treat. Rep. 69: 10071009, 1985. Fifty-six patients with histologically confirmed small cell bronchogenic carcinoma were treated with cyclophosphamide, methotrexate, and etoposide. While methotrexate doses were modified for mucositis during the 6-week induction period, none of the drug doses were modified for hematologic toxicity. The overall response rate was 66%, with 16% complete remissions; median survival duration was 28 weeks. In %2 patients, the leukocyte count fe~l below 1000/mm-, and there were four deaths in febrile, leukopenic pa£ients. Diffuse pulmonary infiltrates were observed in eight patients, and three died from respiratory insufficiency. Lung biopsy in two patients and autopsy in two additional patients showed interstitial changes consistent with drug injury. This regimen produced considerable hematologic and apparent pulmonary toxicity while offering no advantages in response rate or survival duration. Intensive Induction Chemotherapy for Small Cell Anaplastic Carcinoma of the Lung. O'Donnell, M.R., Ruckdeschel, J.C., Baxter, D. et al. Division of Oncology, Albany Medical College, Albany, NY 12208, U.S.A. Cancer Treat. Rep. 69: 571-575, 1985. The role of intensive induction chemotherapy in small cell cancer of the lung remains unclear. Twenty-eight newly diagnosed patients with small cell lung cancer were randomized to receive either high-dose or standard-dose cyclophosphamide, vincristine, and semustine in a trial where the dose of induction chemotherapy was the sole treatment variable. Complete responses (CR) were achieved in 57% of patients receiving high-dose therapy as compared to 21% of patients receiving standard-dose therapy (P < 0.05). There was a higher rate of severe toxicity in the high-dose group (P < 0.01). The over-