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3 Risk of second primary cancers after successful treatment of small cell lung cancer in Spain
3
Therapy - Chemotherapy
Monday, 11 August 1997 ORAL
10:30-l 2:30
SESSION
Chemotherapy
w 1
Phase II trial of navelbine cancer (SCLC)
(NVB), in small cell lung
A. Depierre ‘, T. Le Chevalier*, E. Quoix3, P. Harper4, B. Milleron5, M. Gottfried a, V. Weestel ’ , N. Westerhausen 6, P. Jacoulet ‘, F. Le Bras ‘. ’ CHU Besancon; * Inst. G. Roussy Vikejuif; 3 CHU Strasboug, France, 4Guy!s Hosp London, UK, SCHLJ Tenon Paris, France, 6ST Johanes Hosp. Duisburg, Denmark, 7tnstitut de Recherche Pierre Fabre, France
Aim: NVB has already
shown an increased response rate (RR) in Phase II and phase Ill trials in the management of non-small cell lung cancer (Annals 94, JCO 94). Based on these data, a phase II trial was conducted in order to assess Navelbine in advanced small cell lung cancer patients (pts) previously untreated. Methodology: Pts must have a ECOG Performance Status (PS) of O-2, at least one measurable lesion, adequate organ function, written informed consent. NV6 was administered by weekly injection of 30 mg/m*. Efficacy was assessed every 2 weeks according to WHO criteria. Pts with progressive disease or with stable disease after 6 weeks were switched to second line treatment (CDDPVP16). Pts with objective response continued on NVB until documented confination of response for a maximum of 10 weeks, before being drove to the second line therapy. Patients Characteristics: 27 males, 3 females, all of them with metastatic disease; mean age: 62 (35-77); PS 2: 12 pts (40%); 157 injections of NVB were administered and all patients are evaluable for toxicity and efficacy. Toxicity: The limiting toxicity was myelosupression: 12/30 (40%) developed WHO grade (G) 3-4 leucopenia; 2 pts died due to febrile neutropenia. No thrombocytopenia was observed; 3 pts experienced G3-4 constipation and 1 peripheral neuropathy; G3-4 nausea and vomiting was observed in only 1 pt. Efficacy: RR was 26.7% (95% Cl: 10.9-42.5%); 8 out 30 pts achieved PR after 6 weeks of treatment and all responses were confirmed 4 weeks later. In second line treatment, 25/26 pts were evaluable for response and RR was 46% (95% Cl: 27.9-65%). Conclusion: NVB is effective in SCLC and further trials must be conducted in combination to determine the place of this drug in the treatment of SCLC.
w 2
Factors determining survival in SCLC patients (pts) with complete response to chemotherapy
J. Jassem, A. Badzio, H. Karnicka-Mfodkowska, B. Lisowska, A. Pilarska-Machowicz, R. MoS-Antkowiak, I. Westfal, J. Fabczak. J. Tyrakowska. Polish lung Cancer Cooperative Group, Medical University of Gdansk, Poland The aim of this study was to analyze factors determining survival in SCLC patients with complete response to chemotherapy. Of the 729 SCLC pts included into four consecutive multicenter prospective studies [l-4] complete response to chemotherapy was achieved in 168 (23%). This group included 128 men and 40 women, 91 pts with limited disease and 28 with extensive disease. Median survival time in the entire group of complete responders was 14.8 months. In the univariate analysis prolonged survival correlated with younger age (Cox analysis, p = 0.033). initial performance status (log-rank, p = 0.0313) chemotherapy regimen (log-rank, p = 0.000) and, suprisingly, with delayed complete response (Cox analysis, p = 0.013). No significant correlation was found for gender, initial extent of disease and
weight loss. In the multivariate Cox analysis factors significantly influencing survival included chemotherapy regimen (p = O.OOO), time to complete remission (p = 0.011, in favor of delayed response), initial performance status (p = 0.015) age (0.023) and gender (p = 0.028, in favor of women), whereas initial extent of disease and weight loss remained insignificant. Conclusion: Prognostic factors for survival in SCLC pts with complete response may differ from those observed in the entire population of SCLC pts. [l] [2] [3] [4]
J. J. J. J.
03*
Jassem Jassem Jassem Jassem
et et et et
al. al. al. al.
Pneumonol Pol 1985, 53, 314 Pneum Pol 1988, 56, 142 Eur J Cancer 1992, 26,473 Lung Cancer, 1994, 7 1,283
Risk of second primary cancers after successful treatment of small cell lung cancer in Spain
F. Cardenal, C. Pallares, M. Garcia Martin, R. Mesia, G. Huidobro, A. Montes, P. Maroto, X. Castellsague. Services of Medical Oncology and Cancer Epidemiology, tnstitut CataP d’Onco/ogia and Hospital de Sant Pau, University and Autonomous University of Barcelona, Barcelona, Spain
Background:
American and Japanese investigators have reported that the risk of second primary cancers (SPC) in greater than two-year disease-free survivors of small cell lung cancer (SCLC) is high. Aim: To determine the incidence of SPC following SCLC. Methods: 762 patients treated with standard therapy at our two hospitals from 1980 to 1992 were reviewed to identify those surviving free of SCLC for two or more years after the start of treatment, Forty seven patients were free of cancer two years after initiation of therapy. The median follow-up was.5.7 years. The median survival was 7.75 years (Cl 6.5 to 9 years) Results: Thirteen out of forty seven two-year disease-free survivors subsequently developed fifteen SPC. Seven patients developed second primary lung cancers: two squamous cell, one adeno and one large cell carcinoma, two SCLC (arising in the contralateral lung). One lung cancer was diagnosed on clinical grounds. Three other patients developed squamous cell carcinoma of the head and neck, and another transitional cell carcinoma of the bladder. Other SPC were non-Hodgkin lymphoma, gastric, prostate, and hepatocarcinoma. The cumulative risk of SPC was 55% (Cl 3377%) at ten years. The overall incidence of SPC was 7.4% per patient per year. It increases five times from 3.5% per patient per year during the third and fourth year to 19.8% per patient per year during the seventh and eighth year. Conclusions: We confirm that the risk of SPC (most of them tobaccorelated) is high in long-term survivors of SCLC, higher than in survivors of other cancers. Second primary lung cancers with the same histology of the primary can occur more frequently than has been reported following SCLC.
4 El
Pilot study of cispiatin, doxorubicin, vincristine and etoposide (PAVE) in elderly patients with previously untreated small cell lung cancer (SCLC)
V. Westeel, N. Murray, K. Gelmon, M. McKenzie, F. Wong, J. Morris, C. Grafton, A. Shah, V. Tsang, K. Goddard, K. Murphy, B. Sheehan, C. Parsons, R. Amy, R. Page. Lung Tumor Group, British Columbia Cancer Agency, Vancouver, SC, Canada The PAVE regimen was developed for patients older than 65 years with previously untreated SCLC. PAVE consists of cisplatin 30 mgIm2 IV day 1, doxorubicin 40 ms/ma IV day 1, vincristine 1 .O mgfm* IV day 1, etoposide 100 mg/m2 IV day 1 and PO days 3 and 5. Cycles were repeated at 3-week intervals for 4 treatments. Patients with limited-stage disease (LD) received thoracic irradiation concurrently with etoposide (100 mgIm* IV days 1 to 3) and cisplatin (25 mg/ma IV days 1 to 3) at the time of the second
Therapy - Chemotherapy
Monday, 11 August 1997 ORAL
10:30-l 2:30
SESSION
Chemotherapy
w 1
Phase II trial of navelbine cancer (SCLC)
(NVB), in small cell lung
A. Depierre ‘, T. Le Chevalier*, E. Quoix3, P. Harper4, B. Milleron5, M. Gottfried a, V. Weestel ’ , N. Westerhausen 6, P. Jacoulet ‘, F. Le Bras ‘. ’ CHU Besancon; * Inst. G. Roussy Vikejuif; 3 CHU Strasboug, France, 4Guy!s Hosp London, UK, SCHLJ Tenon Paris, France, 6ST Johanes Hosp. Duisburg, Denmark, 7tnstitut de Recherche Pierre Fabre, France
Aim: NVB has already
shown an increased response rate (RR) in Phase II and phase Ill trials in the management of non-small cell lung cancer (Annals 94, JCO 94). Based on these data, a phase II trial was conducted in order to assess Navelbine in advanced small cell lung cancer patients (pts) previously untreated. Methodology: Pts must have a ECOG Performance Status (PS) of O-2, at least one measurable lesion, adequate organ function, written informed consent. NV6 was administered by weekly injection of 30 mg/m*. Efficacy was assessed every 2 weeks according to WHO criteria. Pts with progressive disease or with stable disease after 6 weeks were switched to second line treatment (CDDPVP16). Pts with objective response continued on NVB until documented confination of response for a maximum of 10 weeks, before being drove to the second line therapy. Patients Characteristics: 27 males, 3 females, all of them with metastatic disease; mean age: 62 (35-77); PS 2: 12 pts (40%); 157 injections of NVB were administered and all patients are evaluable for toxicity and efficacy. Toxicity: The limiting toxicity was myelosupression: 12/30 (40%) developed WHO grade (G) 3-4 leucopenia; 2 pts died due to febrile neutropenia. No thrombocytopenia was observed; 3 pts experienced G3-4 constipation and 1 peripheral neuropathy; G3-4 nausea and vomiting was observed in only 1 pt. Efficacy: RR was 26.7% (95% Cl: 10.9-42.5%); 8 out 30 pts achieved PR after 6 weeks of treatment and all responses were confirmed 4 weeks later. In second line treatment, 25/26 pts were evaluable for response and RR was 46% (95% Cl: 27.9-65%). Conclusion: NVB is effective in SCLC and further trials must be conducted in combination to determine the place of this drug in the treatment of SCLC.
w 2
Factors determining survival in SCLC patients (pts) with complete response to chemotherapy
J. Jassem, A. Badzio, H. Karnicka-Mfodkowska, B. Lisowska, A. Pilarska-Machowicz, R. MoS-Antkowiak, I. Westfal, J. Fabczak. J. Tyrakowska. Polish lung Cancer Cooperative Group, Medical University of Gdansk, Poland The aim of this study was to analyze factors determining survival in SCLC patients with complete response to chemotherapy. Of the 729 SCLC pts included into four consecutive multicenter prospective studies [l-4] complete response to chemotherapy was achieved in 168 (23%). This group included 128 men and 40 women, 91 pts with limited disease and 28 with extensive disease. Median survival time in the entire group of complete responders was 14.8 months. In the univariate analysis prolonged survival correlated with younger age (Cox analysis, p = 0.033). initial performance status (log-rank, p = 0.0313) chemotherapy regimen (log-rank, p = 0.000) and, suprisingly, with delayed complete response (Cox analysis, p = 0.013). No significant correlation was found for gender, initial extent of disease and
weight loss. In the multivariate Cox analysis factors significantly influencing survival included chemotherapy regimen (p = O.OOO), time to complete remission (p = 0.011, in favor of delayed response), initial performance status (p = 0.015) age (0.023) and gender (p = 0.028, in favor of women), whereas initial extent of disease and weight loss remained insignificant. Conclusion: Prognostic factors for survival in SCLC pts with complete response may differ from those observed in the entire population of SCLC pts. [l] [2] [3] [4]
J. J. J. J.
03*
Jassem Jassem Jassem Jassem
et et et et
al. al. al. al.
Pneumonol Pol 1985, 53, 314 Pneum Pol 1988, 56, 142 Eur J Cancer 1992, 26,473 Lung Cancer, 1994, 7 1,283
Risk of second primary cancers after successful treatment of small cell lung cancer in Spain
F. Cardenal, C. Pallares, M. Garcia Martin, R. Mesia, G. Huidobro, A. Montes, P. Maroto, X. Castellsague. Services of Medical Oncology and Cancer Epidemiology, tnstitut CataP d’Onco/ogia and Hospital de Sant Pau, University and Autonomous University of Barcelona, Barcelona, Spain
Background:
American and Japanese investigators have reported that the risk of second primary cancers (SPC) in greater than two-year disease-free survivors of small cell lung cancer (SCLC) is high. Aim: To determine the incidence of SPC following SCLC. Methods: 762 patients treated with standard therapy at our two hospitals from 1980 to 1992 were reviewed to identify those surviving free of SCLC for two or more years after the start of treatment, Forty seven patients were free of cancer two years after initiation of therapy. The median follow-up was.5.7 years. The median survival was 7.75 years (Cl 6.5 to 9 years) Results: Thirteen out of forty seven two-year disease-free survivors subsequently developed fifteen SPC. Seven patients developed second primary lung cancers: two squamous cell, one adeno and one large cell carcinoma, two SCLC (arising in the contralateral lung). One lung cancer was diagnosed on clinical grounds. Three other patients developed squamous cell carcinoma of the head and neck, and another transitional cell carcinoma of the bladder. Other SPC were non-Hodgkin lymphoma, gastric, prostate, and hepatocarcinoma. The cumulative risk of SPC was 55% (Cl 3377%) at ten years. The overall incidence of SPC was 7.4% per patient per year. It increases five times from 3.5% per patient per year during the third and fourth year to 19.8% per patient per year during the seventh and eighth year. Conclusions: We confirm that the risk of SPC (most of them tobaccorelated) is high in long-term survivors of SCLC, higher than in survivors of other cancers. Second primary lung cancers with the same histology of the primary can occur more frequently than has been reported following SCLC.
4 El
Pilot study of cispiatin, doxorubicin, vincristine and etoposide (PAVE) in elderly patients with previously untreated small cell lung cancer (SCLC)
V. Westeel, N. Murray, K. Gelmon, M. McKenzie, F. Wong, J. Morris, C. Grafton, A. Shah, V. Tsang, K. Goddard, K. Murphy, B. Sheehan, C. Parsons, R. Amy, R. Page. Lung Tumor Group, British Columbia Cancer Agency, Vancouver, SC, Canada The PAVE regimen was developed for patients older than 65 years with previously untreated SCLC. PAVE consists of cisplatin 30 mgIm2 IV day 1, doxorubicin 40 ms/ma IV day 1, vincristine 1 .O mgfm* IV day 1, etoposide 100 mg/m2 IV day 1 and PO days 3 and 5. Cycles were repeated at 3-week intervals for 4 treatments. Patients with limited-stage disease (LD) received thoracic irradiation concurrently with etoposide (100 mgIm* IV days 1 to 3) and cisplatin (25 mg/ma IV days 1 to 3) at the time of the second