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Carboplatin, ifosfamide, etoposide and interferon alpha-2A combination chemoimmunotherapy in the treatment of small cell lung carcinoma
Chemotherapy
68
ecog performance status: 0 = 4 (28.6%); 1 = 8 (57.1%); 2 = 2 (14.3%) extensive stage = 9 (64.3%) (2 pts with asintomatic brain metastasis) limited stage = 5 (35.7%). A total of 60 cycles were administered (4.3 per patient-range 1-6), no dose reduction were done; median cycle interval was 23.5 and the dose intensity was 89.36% of the planned dose. Toxicity: All pts were evaluable for toxicity (n = 14). There were no treatment-related death.
their survey. Since our patients number was limited, the data need more patients for this combination.
•]
Paclitaxel-based chemotherapy as second-line treatment in small cell lung cancer (SCLC)
S. Novello, G.V. Scagliotti, G. Selvaggi. University of Torino,
Orbassano, Italy
Response: 12/14 pts were evaluable for response. Two pts have not yet completed the third course of treatment. C.R = 3 pts (25.0%). One was an extensive stage with brain metastasis. A performance status of 0 correlated with response to treatment. P.R = 5 pts (41.7%). O.R. = 66.7%. S.D. = 3 pts (25.0%). P.D = 1 pt (8.3%). All pts have experimented improvement in cancer related symptoms. Conclusion: Topotecan with Ifosfamide plus Mesna is a very active combination in chemotherapy-naive patients with SCLC. General toxicities were mild and hematology toxicities were manageable and short lasting.
From December 1997 to September 1999 sixteen patients with histological diagnosis of SCLC (12 limited disease, 3 extensive disease at diagnosis) received Paclitaxel (P) as single agent 185 mg/m2, day 1, every 3 weeks (9 patients) or in combination with Carboplatin (C) AUC 6 mg/ml/min (Calvertis formula), day 1, every 3 weeks (7 patients). All patients previously received as front-line treatment Cisplatin 6 0 70 mg/m2, day 1 and Etoposide 100 mg/m2, days 1-3, every 3 weeks for an average number of 5 courses and 10 out of 12 patients with limited disease received sequentially thoracic radiotherapy (total dose 45 Gy). At relapse 7 patients were still in limited stage and 8 were re-staged as extensive disease. Other clinical characteristics included: 14 males, 2 females; median age: 60 years (range 5 0 80); ECOG Performance Status 0-2. Median time off-therapy was 8 months (no early relal~ses, <3 months off induction chemotherapy). The total number of courses was 56 (median 3.5), no WHO grade Ill/IV hematologic toxicity was observed; non hematologic toxicities included grade 2 peripheral neuropathy and grade 2 arthralgia/myalgia in 3/16 patients. Response rates in 14 pts evaluable were 0% complete response and 35% partial response (5/14, 3 PR with Paclitaxel single agent and 2 PR with Carboplatin/Paclitaxel), 3 SD and 6 PD. Median survival time from relapse is 28 weeks and 1-year survival is 46%. In conclusion, Paclitaxel-based chemotherapy seems to be a feasible and valuable approach for second-line treatment of patients with relapsing SCLC previously treated with Cisplatin.
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•2--•
grade 1-2 pts [%]
grade 3-4 pts [%]
Hematologic toxicities Neutropenia 7 (49.9) Anemia 4 (28.5) Thrombocytopenia 6 (42.8) Non hematologic toxicities
5 (35.7) 1 (7.1) 3 (21.4)
AIopecia Nausea/vomiting Diarrhea Abdominal pain
9 (64.2) 0 1 (7.1) 0
5 3 4 2
(35.7) (21.4) (28.5) (14.2)
Carboplatin, ifosfamide, etoposide and interferon alpha-2A combination chemoimmunotherepy in the treatment of small cell lung carcinoma
M. Metintas, I. Ucgun, F. Alatas, S. Metintas, E. Harmanci, M. Kolsuz, O. Elbek, A. Yurdasiper, S. Erginel. Osmangazi University Medical
Faculty, Eskisehir, Turkey Aim of this study was to investigate the therapeutic activity and toxicity of combination chemoimmunotherapy with carboplatin, ifosfamide, etoposide, and interferon alpha-2a in a group of patients with histopathologically diagnosed small cell lung carcinoma. Thirty-five patients were enrolled into this study from April 1997 to October 1999. Of the 35 patients, 28 were considered suitable for determining response to therapy, toxicity, and survival time. The remaining 7 patients were not evaluated for response and toxicity because of inadequate followup after one or two courses. Of the patients 18 had extensive disease and 10 had limited disease. The chemoimmunotherapy drug schedule consisted of intravenously administered carboplatin 100 mg/m2 on days 1-3, ifosfamide 1 gm/m2 on days 1-3, etopside 100 mg/m2 on days 1-3 and interferon alpha-2a subcutanously 9 million U weekly. Courses were repeated every four weeks. The response to treatment was determined after the third course of therapy by means of thoracic computer tomography scans, and other investigations were used if indicated. Overall, 149 cycles were administered. A total of 19 objective responses (68%) were assessed; 6 (22%) complete response and 13 (46%) partial. Five (18%) patients had stable disease and 4 (14%) progression. Objective response rate was significantly higher in those with limited disease (9/10:90%) than with extensive disease 10/18:56%). Of the six complete responses, five from limited disease group (5/10:50%) and 1 from extensive disease (1/18:6%). Toxicities were moderate. Drug dose reduction was made in 16 patients and courses were delayed in 8 patients. The drug combination used in our study was effective in response status, but moderately toxic in patients with small cell lung carcinoma. The patients have been following for
Therapy of the small cell lung cancer - Comparison two established chemotherapy regime (ACO vs. CEV)
I. Dittrich, R. Floegel, G. Liebetrau, W.-R. Guschall. Lung Clinic,
D-39291 Lostau, Germany Introduction: Approx. 25% of the malignant epithelial tumors of the lungs are small cell lung cancer. Only a few patients are diagnosed in a tumor stage which allows a primary operation. Therefore the polychemotherapy will remain the first choice of therapy, also in the future, in the predominant number of cases. Method: The validity of a newer chemotherapy regime must be evaluated at the results of established therapy. Standard methods are the ACO (Adriamycin, Cyclophosphamide, Vincristin) and CEV (Carboplatin, Etoposid, Vincristin) scheme. The results of the treatment of patients are in retrospect examined with a small call lung cancer (SCLC) with regard to the related therapy combinations. Results: In the period of 1993 to 1997 a SCLC was diagnosed in 387 patients. 318 (82.2%) of the patients became treated: Operation 4.9%, Radiation 3.6%, Chemotherapy 73.6%. Best supportive care in 17.9% of the cases. 112 patients (35.2%) were treated after the ACO scheme and 98 patients (30.8%) after the CEV scheme.
ACO n (%)
CR ÷ PR LD ED I ED II Age (years)
112 (100) 53 (47.3) 14 (12.5) 31 (27.7) 67 (59.8) 63,2
Mean survival (months) 7.6 11.5 15.7 7.8 4.8
CEV n (%)
98 (100) 67 (68.4) 21 (21.4) 48 (49.0) 29 (29.6) 60.3
Mean survival (months)
Significance
15.0 19.0 26.7 14.4 7.6
0.001 0.064 0.397 0.049 0.049 0.055
68
ecog performance status: 0 = 4 (28.6%); 1 = 8 (57.1%); 2 = 2 (14.3%) extensive stage = 9 (64.3%) (2 pts with asintomatic brain metastasis) limited stage = 5 (35.7%). A total of 60 cycles were administered (4.3 per patient-range 1-6), no dose reduction were done; median cycle interval was 23.5 and the dose intensity was 89.36% of the planned dose. Toxicity: All pts were evaluable for toxicity (n = 14). There were no treatment-related death.
their survey. Since our patients number was limited, the data need more patients for this combination.
•]
Paclitaxel-based chemotherapy as second-line treatment in small cell lung cancer (SCLC)
S. Novello, G.V. Scagliotti, G. Selvaggi. University of Torino,
Orbassano, Italy
Response: 12/14 pts were evaluable for response. Two pts have not yet completed the third course of treatment. C.R = 3 pts (25.0%). One was an extensive stage with brain metastasis. A performance status of 0 correlated with response to treatment. P.R = 5 pts (41.7%). O.R. = 66.7%. S.D. = 3 pts (25.0%). P.D = 1 pt (8.3%). All pts have experimented improvement in cancer related symptoms. Conclusion: Topotecan with Ifosfamide plus Mesna is a very active combination in chemotherapy-naive patients with SCLC. General toxicities were mild and hematology toxicities were manageable and short lasting.
From December 1997 to September 1999 sixteen patients with histological diagnosis of SCLC (12 limited disease, 3 extensive disease at diagnosis) received Paclitaxel (P) as single agent 185 mg/m2, day 1, every 3 weeks (9 patients) or in combination with Carboplatin (C) AUC 6 mg/ml/min (Calvertis formula), day 1, every 3 weeks (7 patients). All patients previously received as front-line treatment Cisplatin 6 0 70 mg/m2, day 1 and Etoposide 100 mg/m2, days 1-3, every 3 weeks for an average number of 5 courses and 10 out of 12 patients with limited disease received sequentially thoracic radiotherapy (total dose 45 Gy). At relapse 7 patients were still in limited stage and 8 were re-staged as extensive disease. Other clinical characteristics included: 14 males, 2 females; median age: 60 years (range 5 0 80); ECOG Performance Status 0-2. Median time off-therapy was 8 months (no early relal~ses, <3 months off induction chemotherapy). The total number of courses was 56 (median 3.5), no WHO grade Ill/IV hematologic toxicity was observed; non hematologic toxicities included grade 2 peripheral neuropathy and grade 2 arthralgia/myalgia in 3/16 patients. Response rates in 14 pts evaluable were 0% complete response and 35% partial response (5/14, 3 PR with Paclitaxel single agent and 2 PR with Carboplatin/Paclitaxel), 3 SD and 6 PD. Median survival time from relapse is 28 weeks and 1-year survival is 46%. In conclusion, Paclitaxel-based chemotherapy seems to be a feasible and valuable approach for second-line treatment of patients with relapsing SCLC previously treated with Cisplatin.
~-]
•2--•
grade 1-2 pts [%]
grade 3-4 pts [%]
Hematologic toxicities Neutropenia 7 (49.9) Anemia 4 (28.5) Thrombocytopenia 6 (42.8) Non hematologic toxicities
5 (35.7) 1 (7.1) 3 (21.4)
AIopecia Nausea/vomiting Diarrhea Abdominal pain
9 (64.2) 0 1 (7.1) 0
5 3 4 2
(35.7) (21.4) (28.5) (14.2)
Carboplatin, ifosfamide, etoposide and interferon alpha-2A combination chemoimmunotherepy in the treatment of small cell lung carcinoma
M. Metintas, I. Ucgun, F. Alatas, S. Metintas, E. Harmanci, M. Kolsuz, O. Elbek, A. Yurdasiper, S. Erginel. Osmangazi University Medical
Faculty, Eskisehir, Turkey Aim of this study was to investigate the therapeutic activity and toxicity of combination chemoimmunotherapy with carboplatin, ifosfamide, etoposide, and interferon alpha-2a in a group of patients with histopathologically diagnosed small cell lung carcinoma. Thirty-five patients were enrolled into this study from April 1997 to October 1999. Of the 35 patients, 28 were considered suitable for determining response to therapy, toxicity, and survival time. The remaining 7 patients were not evaluated for response and toxicity because of inadequate followup after one or two courses. Of the patients 18 had extensive disease and 10 had limited disease. The chemoimmunotherapy drug schedule consisted of intravenously administered carboplatin 100 mg/m2 on days 1-3, ifosfamide 1 gm/m2 on days 1-3, etopside 100 mg/m2 on days 1-3 and interferon alpha-2a subcutanously 9 million U weekly. Courses were repeated every four weeks. The response to treatment was determined after the third course of therapy by means of thoracic computer tomography scans, and other investigations were used if indicated. Overall, 149 cycles were administered. A total of 19 objective responses (68%) were assessed; 6 (22%) complete response and 13 (46%) partial. Five (18%) patients had stable disease and 4 (14%) progression. Objective response rate was significantly higher in those with limited disease (9/10:90%) than with extensive disease 10/18:56%). Of the six complete responses, five from limited disease group (5/10:50%) and 1 from extensive disease (1/18:6%). Toxicities were moderate. Drug dose reduction was made in 16 patients and courses were delayed in 8 patients. The drug combination used in our study was effective in response status, but moderately toxic in patients with small cell lung carcinoma. The patients have been following for
Therapy of the small cell lung cancer - Comparison two established chemotherapy regime (ACO vs. CEV)
I. Dittrich, R. Floegel, G. Liebetrau, W.-R. Guschall. Lung Clinic,
D-39291 Lostau, Germany Introduction: Approx. 25% of the malignant epithelial tumors of the lungs are small cell lung cancer. Only a few patients are diagnosed in a tumor stage which allows a primary operation. Therefore the polychemotherapy will remain the first choice of therapy, also in the future, in the predominant number of cases. Method: The validity of a newer chemotherapy regime must be evaluated at the results of established therapy. Standard methods are the ACO (Adriamycin, Cyclophosphamide, Vincristin) and CEV (Carboplatin, Etoposid, Vincristin) scheme. The results of the treatment of patients are in retrospect examined with a small call lung cancer (SCLC) with regard to the related therapy combinations. Results: In the period of 1993 to 1997 a SCLC was diagnosed in 387 patients. 318 (82.2%) of the patients became treated: Operation 4.9%, Radiation 3.6%, Chemotherapy 73.6%. Best supportive care in 17.9% of the cases. 112 patients (35.2%) were treated after the ACO scheme and 98 patients (30.8%) after the CEV scheme.
ACO n (%)
CR ÷ PR LD ED I ED II Age (years)
112 (100) 53 (47.3) 14 (12.5) 31 (27.7) 67 (59.8) 63,2
Mean survival (months) 7.6 11.5 15.7 7.8 4.8
CEV n (%)
98 (100) 67 (68.4) 21 (21.4) 48 (49.0) 29 (29.6) 60.3
Mean survival (months)
Significance
15.0 19.0 26.7 14.4 7.6
0.001 0.064 0.397 0.049 0.049 0.055