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Gemcitabine (G), ifosfamide (I), vinorelbine (N) in advanced non small cell lung cancer: A phase II study
Chemotherapy~Mix I1 1 (01 Gemcitabine (G), ifosfamide (I), vinorelbine (N) in advanced non small cell lung cancer: A phase II study
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J.E Morere, MC. Pailler, T. Bouillet, S. Piperno-Neumann, C. Blanchard, MA. Coulon, O. Fain, F. Hennebelle, J.L. Breau.
Avicenne Hospital, Bobigny, France Background: The ifosfamide-vinorelbine double combination was tested in a previous phase II study with a 30% response rate. Gemcitabine is a recent anticancer drug that exhibits a novel mechanism of action and good efficacy toxicity profile. Methods: In May 1998, we initiated a Phase II study to evaluate the activity of the triple GIN, platinum-free regimen. Gemcitabine was given at a dose of 1000 mg/m 2 on D1 and D15, ifosfamide 1.5 g/m 2 from D1 to D3 and vinorelbine 25 mg/m 2 on D1 and D15, one course every 28 days. Inclusion criteria included, measurable stage III or IV NSCLC, PS = 2, normal blood count and chemistries. Results: A total of 30 patients, 25 males and 5 females, were included. Characteristics of the population are the following: median age 60 yo (range 40-72), stage IIIB 15, stage IV 15, PS 0 in 4 pts, 1 in 23 pts and 2 in 3 pts, squamous cell carcinoma 12, adenocarcinoma 16, large cell carcinoma 2. Median number of cycles was 4. Among 28 pts evaluable for toxicity, 43% experienced grade III or IV neutropenia, only one patient had a febrile neutropenia. No pt received prophylactic or curative G-CSF. Nausea and vomiting were severe in 7% of pts, 12 patients presented with grade II asthenia. Nine objective responses among 27 evaluable pts (33%, CI 29-36%) and 8 stabilisations (29%) were achieved, 2 stage IIIb patients could be operated on later. No relevant difference was observed in response rates according to stage or histological subtypes. Median survival is 10 months with a 1 year survival of 49%. Conclusion: GIN is a well tolerated ambulatory regimen in the management of advanced NSCLC.
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Vinorelbine, ifosfamide and cisplatin (NIP) as first line chemotherapy in patients with non-small-cell lung cancer (NSCLC)
37
Treatment results of vinorelbine (VIN) and carboplatinum (CAR) in unselected patients with non-small-cell lung cancer (NSCLC) - Analysis by means of a clinical tumor registry
F.J.H. yon Bueltzingsloewen. Fachklinik Donaustauf, 93093
Donaustauf, Germany Since November 1996 139 pts were treated outside of clinical studies with 30 mg/m2 VIN on days 1 and 8 and CAR AUC 5 on day 1 i.v. q 3 weekly. Using our tumor registry 119 pts (336 cycles) were analysed. Histologies: 76 squamous cell, 50 adeno, 7 large cell and 5 various. Stages (UICC98): IA 1, IB 6, IIA 2, liB 12, IliA 19, IIIB 37 (27%) and IV 60 (43%). Sequence of chemotherapy: 20 adjuvant postoperative, 103 first-line and 16 second-line cases. Cycle (cy) numbers: 1 cy 25 pts, 2 cy 37, 3 cy 22 (16%) and 4 cy 55 lots (40%). Hematological toxicity (225 cycles): no anemia, leucopenia or thrombocytopenia in 174 (67.1%), 101 (38.9%) and 253 cy (97.6%), anemia grade 1/11in 77 (29.6%), grade Ill/IV in 8 cy, leucopenia grade 1/11in 98 (37.7%), grade Ill/IV in 60 cy (23.1%), thrombocytopenia grade 1/11in 4, grade Ill/IV in 2. Non-hematological (119 pts): Nausea/vomiting grade 1/11in 35 pts (29.4%), grade III in 6 pts, obstipation grade 1/1127 pts (22.6%), grade III 5 pts, stomatitis grade 1/1123 pts (19.2%), grade III 2 pts, alopecia grade 1/1133 pts (27.6%), grade III one pt, central nervous side effects 30 pts (25.1%), grade III one pt, peripheral neurotoxicity grade 1/1120 pts (16.7%), grade III one pt, fever or infection grade I/ll 22 pts (18.3%), grade III 9 pts (7.5%) and grade IV one pt, other toxicities grade 1/1124 pts (20%) and grade III 7 pts (5.8%), 2 therapy-related deaths. Remission rates (100 pts first-line chemotherapy with 2 pts each stages Iund II, 13 pts stage IliA, 34 pts stage IIIB and 49 stage IV): 14 PR, 70 NC/MR, 16 progressing with no correlation between remission and survival. Survival: 48 pts died, MST 5,1 months, TTP 7.4 months, DFS 14.1 months, 1-y-survival rate stage IIIB/IV (83) 42%. 30% of this group alive at 30 months. Conclusion: Treatment of NSCLC with VIN and CAR is generally well tolerated. There was no correlation between remission rate and survival. One-year survival rate of stages IIIB or IV is encouraging with 42% and 30% pts alive at 30 months.
E. Teixeira, R. Sotto-Mayor, M. Borges, A. Bugalho de Almeida.
Hospital Santa Maria, Lisbon, Portugal Purpose: The aim of this study is to present the results of a consecutive series of patients (pts) with locally advanced/metastatic NSCLC, treated with NIP, in the clinical practice. Patients and Methods: Thirty chemotherapy nai"ve patients with NSCLC were treated with vinorelbine (25 mg/m2 day 1 and day 8), ifosfamide (3 g/m2 day 1 with uroprotective mesna), and cisplatin (80 mg/m2 day 1) every 3 weeks. G-CSF support was given according to clinical judgment. Four (2%) pts had stade IliA, nineteen (70%) had stage IIIB and 7 (30%) had stage IV disease. Most of the patients (26) had a WHO performance status of 0/1; the predominant histologic type was squamous cell carcinoma (13 pts). All patients were included in the analysis (intent-to-treat). Results: Thirteen pts (44.3%) (CI 95% 25.5-62.6%) achieved a partial response to treatment. The median duration of response was 8.4 weeks and the median overall survival was 53.9 weeks. The 1year survival rate was 53.2% (IC 95% 28.0 - 73.1%). A total of 95 courses of therapy were given (median 3 cycles/patient). Grade 3 or 4 neutropenia occurred in 40% of administered courses (38 out of 95 courses). Other acute side effects were relatively mild. Conclusions: NIP regime seems to be useful in the management of NSCLC in the current clinical practice.
Thursday, 14 S e p t e m b e r 2000
8:30-10:00
ORAL SESSION
Chemotherapy/Mix
•1-•
Combined chemotherapy with AVP (Nidran + Vepasid + Cisplatin) in patients with extensive lung cancer
M.B. Bychkov, V.A. Gorbunova, A.F. Marenich, D.R. Naschletashvili.
Cancer Research Center RAMS, Moscow, Russia Aim: To evaluate the efficacy of new combined chemotherapy AVP in patients with extensive lung cancer. Patients and Methods: 45 previously untreated patients with morphologically proven SCLC and 25 previously untreated patients with morphologically proven NSCLC were treated with AVP: Nidran (ACNU) 3 mg/kg i.v. day 1 + Vepesid 100 rag/rag i.v. day 4, 5, 6 + Cisplatin 40 mg/mq i.v. day 2, 8 every 6 weeks. The patients range in age from 30 to 71 (median age 61), the WHO performanse status - 0-2. All patients were evaluable for response rate (CT, X-ray, Ultrasound). Results: SCLC - overall response rate was 60% (27145): 5 complete responses (11%) and 22 partial responses (49%). Responses on distant metastases were: brain - 11/15 (73%, 8/15 - (CR) complete response), liver - 8/11 (72%, 3/11 - CR), adrenal glands - 5/10 (50%, 1/10 - CR), bones - 4/8 (50%, 1/8 - CR). It was showed the improvement of survival patients, receiving chemotherapy with AVP (12.7 months) in comparison with survival patients, receiving other schemes chemotherapy - CAV, ACE (8.8 months).
I••
J.E Morere, MC. Pailler, T. Bouillet, S. Piperno-Neumann, C. Blanchard, MA. Coulon, O. Fain, F. Hennebelle, J.L. Breau.
Avicenne Hospital, Bobigny, France Background: The ifosfamide-vinorelbine double combination was tested in a previous phase II study with a 30% response rate. Gemcitabine is a recent anticancer drug that exhibits a novel mechanism of action and good efficacy toxicity profile. Methods: In May 1998, we initiated a Phase II study to evaluate the activity of the triple GIN, platinum-free regimen. Gemcitabine was given at a dose of 1000 mg/m 2 on D1 and D15, ifosfamide 1.5 g/m 2 from D1 to D3 and vinorelbine 25 mg/m 2 on D1 and D15, one course every 28 days. Inclusion criteria included, measurable stage III or IV NSCLC, PS = 2, normal blood count and chemistries. Results: A total of 30 patients, 25 males and 5 females, were included. Characteristics of the population are the following: median age 60 yo (range 40-72), stage IIIB 15, stage IV 15, PS 0 in 4 pts, 1 in 23 pts and 2 in 3 pts, squamous cell carcinoma 12, adenocarcinoma 16, large cell carcinoma 2. Median number of cycles was 4. Among 28 pts evaluable for toxicity, 43% experienced grade III or IV neutropenia, only one patient had a febrile neutropenia. No pt received prophylactic or curative G-CSF. Nausea and vomiting were severe in 7% of pts, 12 patients presented with grade II asthenia. Nine objective responses among 27 evaluable pts (33%, CI 29-36%) and 8 stabilisations (29%) were achieved, 2 stage IIIb patients could be operated on later. No relevant difference was observed in response rates according to stage or histological subtypes. Median survival is 10 months with a 1 year survival of 49%. Conclusion: GIN is a well tolerated ambulatory regimen in the management of advanced NSCLC.
•1•
Vinorelbine, ifosfamide and cisplatin (NIP) as first line chemotherapy in patients with non-small-cell lung cancer (NSCLC)
37
Treatment results of vinorelbine (VIN) and carboplatinum (CAR) in unselected patients with non-small-cell lung cancer (NSCLC) - Analysis by means of a clinical tumor registry
F.J.H. yon Bueltzingsloewen. Fachklinik Donaustauf, 93093
Donaustauf, Germany Since November 1996 139 pts were treated outside of clinical studies with 30 mg/m2 VIN on days 1 and 8 and CAR AUC 5 on day 1 i.v. q 3 weekly. Using our tumor registry 119 pts (336 cycles) were analysed. Histologies: 76 squamous cell, 50 adeno, 7 large cell and 5 various. Stages (UICC98): IA 1, IB 6, IIA 2, liB 12, IliA 19, IIIB 37 (27%) and IV 60 (43%). Sequence of chemotherapy: 20 adjuvant postoperative, 103 first-line and 16 second-line cases. Cycle (cy) numbers: 1 cy 25 pts, 2 cy 37, 3 cy 22 (16%) and 4 cy 55 lots (40%). Hematological toxicity (225 cycles): no anemia, leucopenia or thrombocytopenia in 174 (67.1%), 101 (38.9%) and 253 cy (97.6%), anemia grade 1/11in 77 (29.6%), grade Ill/IV in 8 cy, leucopenia grade 1/11in 98 (37.7%), grade Ill/IV in 60 cy (23.1%), thrombocytopenia grade 1/11in 4, grade Ill/IV in 2. Non-hematological (119 pts): Nausea/vomiting grade 1/11in 35 pts (29.4%), grade III in 6 pts, obstipation grade 1/1127 pts (22.6%), grade III 5 pts, stomatitis grade 1/1123 pts (19.2%), grade III 2 pts, alopecia grade 1/1133 pts (27.6%), grade III one pt, central nervous side effects 30 pts (25.1%), grade III one pt, peripheral neurotoxicity grade 1/1120 pts (16.7%), grade III one pt, fever or infection grade I/ll 22 pts (18.3%), grade III 9 pts (7.5%) and grade IV one pt, other toxicities grade 1/1124 pts (20%) and grade III 7 pts (5.8%), 2 therapy-related deaths. Remission rates (100 pts first-line chemotherapy with 2 pts each stages Iund II, 13 pts stage IliA, 34 pts stage IIIB and 49 stage IV): 14 PR, 70 NC/MR, 16 progressing with no correlation between remission and survival. Survival: 48 pts died, MST 5,1 months, TTP 7.4 months, DFS 14.1 months, 1-y-survival rate stage IIIB/IV (83) 42%. 30% of this group alive at 30 months. Conclusion: Treatment of NSCLC with VIN and CAR is generally well tolerated. There was no correlation between remission rate and survival. One-year survival rate of stages IIIB or IV is encouraging with 42% and 30% pts alive at 30 months.
E. Teixeira, R. Sotto-Mayor, M. Borges, A. Bugalho de Almeida.
Hospital Santa Maria, Lisbon, Portugal Purpose: The aim of this study is to present the results of a consecutive series of patients (pts) with locally advanced/metastatic NSCLC, treated with NIP, in the clinical practice. Patients and Methods: Thirty chemotherapy nai"ve patients with NSCLC were treated with vinorelbine (25 mg/m2 day 1 and day 8), ifosfamide (3 g/m2 day 1 with uroprotective mesna), and cisplatin (80 mg/m2 day 1) every 3 weeks. G-CSF support was given according to clinical judgment. Four (2%) pts had stade IliA, nineteen (70%) had stage IIIB and 7 (30%) had stage IV disease. Most of the patients (26) had a WHO performance status of 0/1; the predominant histologic type was squamous cell carcinoma (13 pts). All patients were included in the analysis (intent-to-treat). Results: Thirteen pts (44.3%) (CI 95% 25.5-62.6%) achieved a partial response to treatment. The median duration of response was 8.4 weeks and the median overall survival was 53.9 weeks. The 1year survival rate was 53.2% (IC 95% 28.0 - 73.1%). A total of 95 courses of therapy were given (median 3 cycles/patient). Grade 3 or 4 neutropenia occurred in 40% of administered courses (38 out of 95 courses). Other acute side effects were relatively mild. Conclusions: NIP regime seems to be useful in the management of NSCLC in the current clinical practice.
Thursday, 14 S e p t e m b e r 2000
8:30-10:00
ORAL SESSION
Chemotherapy/Mix
•1-•
Combined chemotherapy with AVP (Nidran + Vepasid + Cisplatin) in patients with extensive lung cancer
M.B. Bychkov, V.A. Gorbunova, A.F. Marenich, D.R. Naschletashvili.
Cancer Research Center RAMS, Moscow, Russia Aim: To evaluate the efficacy of new combined chemotherapy AVP in patients with extensive lung cancer. Patients and Methods: 45 previously untreated patients with morphologically proven SCLC and 25 previously untreated patients with morphologically proven NSCLC were treated with AVP: Nidran (ACNU) 3 mg/kg i.v. day 1 + Vepesid 100 rag/rag i.v. day 4, 5, 6 + Cisplatin 40 mg/mq i.v. day 2, 8 every 6 weeks. The patients range in age from 30 to 71 (median age 61), the WHO performanse status - 0-2. All patients were evaluable for response rate (CT, X-ray, Ultrasound). Results: SCLC - overall response rate was 60% (27145): 5 complete responses (11%) and 22 partial responses (49%). Responses on distant metastases were: brain - 11/15 (73%, 8/15 - (CR) complete response), liver - 8/11 (72%, 3/11 - CR), adrenal glands - 5/10 (50%, 1/10 - CR), bones - 4/8 (50%, 1/8 - CR). It was showed the improvement of survival patients, receiving chemotherapy with AVP (12.7 months) in comparison with survival patients, receiving other schemes chemotherapy - CAV, ACE (8.8 months).