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207 Carboplatin and etoposide in the treatment of elderly small cell lung cancer (SCLC)
54 12051 Phase i-11 study of vinorelbine (VNR), cisplatin (CDDP) and mitomycin C (MMC) in non-small cell lung cancer (NSCLC) M. Ogawara r, K. Furuse’, Y. Nishiwaki’, ’ Nat/. Kinki-Central Hosp., Sakai, Osaka; East; 30saka Prefectural Habikino Hasp; Osaka, Japan
M. Takada3, M. Fukuoka4. 2Natl. Cancer Center Hosp. 40saka Cify Genera/ Hosp.,
VNR, a novel semi-synthetic vinca alkaloid, is highly active in NSCLC patients (pts). Phase I-II study of VNR (20-25 mg/m’) with CDDP (80 mg/m2), and MMC (4 to 8 mg/m2) was conducted in previously untreated stage IIIB/IV NSCLC pts. VNR was administered on day 1 and 8, and CDDP and MMC on day 1. The second course was started after 4 weeks and the further courses were repeated every 6 weeks. In phase I, leukopenia was considered to be dose-limiting toxicity. In level 4 (VNR 25 mg/m2, CDDP 80 mg/m’, MMC 8 mg/ms), 2/9 pts experienced grade 4 leukopenia over 4 days. Level 4 doses were recommended for phase II study. In phase II, grade 4 leukopenia over 4 days developed in 2/19 pts. Grade 3 toxicity of GPT, constipation and stomatitis appeared in i/19, l/19 and 2/19 pts, respectively. 29 pts responded among 46 eligible pts with overall rate 58.7% (95% Cl;43.2-73.0). 46 eligible pts were entered including 27 for 63 phase f and 19 for phase’ II, 28 males’and 17 females, median-age (range 49-75) 19 at stage IIIB and 27 at stage IV, 41 PSI-1 and 5 PS4. Out bf 29 pts in level 4 ;n phase I-II study, 1 achieved CR and 19 PR, resulting overall response rate 69.0% (95%Cl; 49.2-84.7). As the level 4 of the combination is shown to be manageable and highly active against untreated stage IIIB/IV NSCLC, the comparative study of this regimen with the combination of vindesine, CDDP and MMC is planned.
I206
Treatment of limited small cell lung cancer (SCLC) with paclitaxel, cisplatin, etoposide and radiation therapy
R.M. Bremnes’, S. Sundstrem2, U. Aasebe3, J. Vilsvik4. Deptsof ’ Oncology; 3 Chest medicine, Univ Hospital of Tromsn; Depts of 2 Oncology; 4 Chest medicine, Univ. hospifal of Trondheim, Norway In March 1998 we initiated a phase II study in patients with limited SCLC in order to investigate the efficacy and toxicity of a novel combination regimen including paclitaxel (i-hour infusion), cisplatin, etoposide, and concurrent thoracic irradiation. Entry criteria included: PS 0, 1, or 2, no previous chemo- or radiotherapy, adequate liver and kidney function, measurable disease, and informed consent. So far 13 patients have been included. The median age is 66 years and 69% are male. The PS was good (PS O-9 patients, PS 14 patients). The median tumour size was 6.5 cm. The patients received 5 courses of chemotherapy (paclitaxel 175 mg/m* as IV infusion day 1, cisplatin 50 mg/m* IV day 1, etoposide 100 mg/m’ IV day 1, and oral etoposide 100 mg bid day 2-5) at three week intervals. Concurrent thoracic radiotherapy (42 Gy/15 fractions) was started with the third chemotherapy cycle (week 6). Patients obtaining complete remission (CR) received prophylactic cranial radiation (30 Gy/l5 fractions) after completion of the chemotherapy treatment. Eight patients have completed the chemotherapy treatment. Median follow up after completion of chemotherapy is 5 months. All evaluable patients responded to treatment (PFUCR). Seven of 8 patients (88%) achieved CR, and are progression-free. The one patient that failed to achieve CR (initial tumour size of 10 cm) obtained a near complete remission, but has later progressed. No hypersensitivity reaction occurred. Four patients experienced grade 3 or 4 leucopenia after course 1. There was one treatment related death due to severe neutropenia. There was no grade 3 or 4 trombocytopenia. Chemotherapy doses were reduced in 49% (mean) of courses 2,3,4. and 5. Three patients developed completely reversible grade 3 neuropathy, and there was one report of grade 3 myalgia. One patient developed grade 3 esophagitis during radiotherapy. This treatment appears to be a highly active and relatively well tolerated regimen.
12071 Carboplatin and etoposide in the treatment small cell lung cancer (SCLC)
of elderly
K. Shibata, K. Kasahara, Y. Nakatsumi, T. Bando, M. Fujimura, T. Matsuda. Dep. of lntemal Medicine (I/), Kanazawa Univ. Sch. Medicine, Kanazawa, Japan We conducted a pilot phase II study to evaluate the activity and toxicity of the combination of carboplatin and etoposide in the treatment of elderly SCLC patients (pts). Eligibility criteria included histologically proven SCLC, no prior therapy, age 270, ECOG performance status (PS) 52, adequate organ functions and informed consent. Carboplatin 100 mg/ms (75 mg/m2 if Ccr ~60) IV on day 1,3 and 5 and etoposide 70 mg/m2 IV on days 1 to 5 were administered every 3-4 wks. Filgrastim was given subcutaneouosly everyday from day 6 until the full leukocyte recovery. 25 pts. were entered and 22 pts. (8 LD, 14 ED) were eligible. Median age was 78 (range: 70-82) and PS was O/l in 16 pts. The most common toxicities were hematological. Ten (45%) and seven (32%) pts. experienced G3/4 neutropenia and thrombocytopenia, respectively. Non-hematological toxicities were mild. One patient died of sepsis associated with neutropenia. 21 pts. were evaluable for response. 17 objective responses (7 LD, 10 ED) including 5 CR (3 LD, 2 ED) were observed. The overall response rate was 81% (95%CI: 58-95%) and the CR rate was 24% (8-47%). The response rates of LD and ED were 88% (47-100%) and 77% (54-95%) respectively. The median progression free survival was 5.7 months (M) (LD 7.3 M, ED 5.7 M). The median overall survival was 9.8 M (LD 11.2 M, ED 8.7 M). We concluded this regimen is feasible for elderly SCLC.
12081 Neoadjuvant chemotherapy ifosfamide etoposide and cisplatin (VIP) in 50 patients with non small cell lung cancer (NSCLC) D. Roux ‘, M. Taiar’, J.O. Bay’, F. Kwiatkowski ‘, G. Escande”, E. Bardet 3, P. Verrelle ‘. ’ Centre J. Perrin, Clermont-Ferrand; 2C.H.U. G. Montpied, Clermont-Fenand; 3Centre 13. Gauducheau, Nantes, France From February 1990 to April 1996, we treated 50 locally advanced (MO) or metastatic (Ml) NSCLC patients (pts) with the same regimen as a neoadjuvant or induction chemotherapy. The treatment consisted in etoposide (75 ms/ms), cisplatinum (25 mg/m2) and ifosfamide (1.5 g/m’). These drugs were administered IV from day 1 to day 4 (dl to d28) for 2 courses or more (mean: 3 courses/patient). 46 pts received at least 2 courses. For all evaluable pts, the intrathoracic response was evaluated after 2 courses, only the MO responders had a third course prior to local treatment (radiation therapy or surgery). The median follow up is 21 months, Pretreatment Patient Characteristics: 44 male/6 female; mean age: 59 years; WHO performance status O-l: 33, 2-3: 17; 1 stage II, 11 stage IIIA, 15 stage 1118, 23 stage IV; 31 squamous cell, 9 adenocarcinoma, 6 indifferenciated and 4 large cell carcinoma. Toxicity: 8 of the 149 delivered courses led to grade Ill or IV hematologic toxicity. 1 patient died because of a pulmonary infection during aplasia. We never used hematopoietic growth factors. Results: 4/50 pts died early, 3 of them because of a disease progression and 1 because of toxicity. 44/46 were’evaluable with one complete response and 25 partial response (overall response: 59%). 26 MO pts were evaluable and we observed 15 responses (58%); 18 Ml pts were evaluable, 11 were responders (61%) but the high number of Tl-T2 in Ml pts explains the good thoracic response. 9 pts had surgery (4 stage IIIA, 3 stage IIIB and 2 stage IV with brain metastasis). 2 of them died right after. Survival: the median survival rate is 11 months forthe 50 pts, 14 months for the 27 MO pts, 6.5 months for the 23 Ml pts. The overall survival is 48% at 1 year and 30% at 2 years. For MO pts, 66.5% at 1 year, 42.4% at 2 years; for Ml pts 26.1% at 1 year, 13.9% at 2 years. Regarding the most important prognosis factors we observed that survival was significantly correlated with response rate, performance status and more strongly to the first one. Conclusion: VIP regimen is well tolerated with an interesting thoracic response rate in our population of non selected pts with advanced NSCLC. Randomised studies should be needed to compare the VIP efficacy to that of the other neoadjuvant treatment modalities without omitting quality of life evaluation.
M. Takada3, M. Fukuoka4. 2Natl. Cancer Center Hosp. 40saka Cify Genera/ Hosp.,
VNR, a novel semi-synthetic vinca alkaloid, is highly active in NSCLC patients (pts). Phase I-II study of VNR (20-25 mg/m’) with CDDP (80 mg/m2), and MMC (4 to 8 mg/m2) was conducted in previously untreated stage IIIB/IV NSCLC pts. VNR was administered on day 1 and 8, and CDDP and MMC on day 1. The second course was started after 4 weeks and the further courses were repeated every 6 weeks. In phase I, leukopenia was considered to be dose-limiting toxicity. In level 4 (VNR 25 mg/m2, CDDP 80 mg/m’, MMC 8 mg/ms), 2/9 pts experienced grade 4 leukopenia over 4 days. Level 4 doses were recommended for phase II study. In phase II, grade 4 leukopenia over 4 days developed in 2/19 pts. Grade 3 toxicity of GPT, constipation and stomatitis appeared in i/19, l/19 and 2/19 pts, respectively. 29 pts responded among 46 eligible pts with overall rate 58.7% (95% Cl;43.2-73.0). 46 eligible pts were entered including 27 for 63 phase f and 19 for phase’ II, 28 males’and 17 females, median-age (range 49-75) 19 at stage IIIB and 27 at stage IV, 41 PSI-1 and 5 PS4. Out bf 29 pts in level 4 ;n phase I-II study, 1 achieved CR and 19 PR, resulting overall response rate 69.0% (95%Cl; 49.2-84.7). As the level 4 of the combination is shown to be manageable and highly active against untreated stage IIIB/IV NSCLC, the comparative study of this regimen with the combination of vindesine, CDDP and MMC is planned.
I206
Treatment of limited small cell lung cancer (SCLC) with paclitaxel, cisplatin, etoposide and radiation therapy
R.M. Bremnes’, S. Sundstrem2, U. Aasebe3, J. Vilsvik4. Deptsof ’ Oncology; 3 Chest medicine, Univ Hospital of Tromsn; Depts of 2 Oncology; 4 Chest medicine, Univ. hospifal of Trondheim, Norway In March 1998 we initiated a phase II study in patients with limited SCLC in order to investigate the efficacy and toxicity of a novel combination regimen including paclitaxel (i-hour infusion), cisplatin, etoposide, and concurrent thoracic irradiation. Entry criteria included: PS 0, 1, or 2, no previous chemo- or radiotherapy, adequate liver and kidney function, measurable disease, and informed consent. So far 13 patients have been included. The median age is 66 years and 69% are male. The PS was good (PS O-9 patients, PS 14 patients). The median tumour size was 6.5 cm. The patients received 5 courses of chemotherapy (paclitaxel 175 mg/m* as IV infusion day 1, cisplatin 50 mg/m* IV day 1, etoposide 100 mg/m’ IV day 1, and oral etoposide 100 mg bid day 2-5) at three week intervals. Concurrent thoracic radiotherapy (42 Gy/15 fractions) was started with the third chemotherapy cycle (week 6). Patients obtaining complete remission (CR) received prophylactic cranial radiation (30 Gy/l5 fractions) after completion of the chemotherapy treatment. Eight patients have completed the chemotherapy treatment. Median follow up after completion of chemotherapy is 5 months. All evaluable patients responded to treatment (PFUCR). Seven of 8 patients (88%) achieved CR, and are progression-free. The one patient that failed to achieve CR (initial tumour size of 10 cm) obtained a near complete remission, but has later progressed. No hypersensitivity reaction occurred. Four patients experienced grade 3 or 4 leucopenia after course 1. There was one treatment related death due to severe neutropenia. There was no grade 3 or 4 trombocytopenia. Chemotherapy doses were reduced in 49% (mean) of courses 2,3,4. and 5. Three patients developed completely reversible grade 3 neuropathy, and there was one report of grade 3 myalgia. One patient developed grade 3 esophagitis during radiotherapy. This treatment appears to be a highly active and relatively well tolerated regimen.
12071 Carboplatin and etoposide in the treatment small cell lung cancer (SCLC)
of elderly
K. Shibata, K. Kasahara, Y. Nakatsumi, T. Bando, M. Fujimura, T. Matsuda. Dep. of lntemal Medicine (I/), Kanazawa Univ. Sch. Medicine, Kanazawa, Japan We conducted a pilot phase II study to evaluate the activity and toxicity of the combination of carboplatin and etoposide in the treatment of elderly SCLC patients (pts). Eligibility criteria included histologically proven SCLC, no prior therapy, age 270, ECOG performance status (PS) 52, adequate organ functions and informed consent. Carboplatin 100 mg/ms (75 mg/m2 if Ccr ~60) IV on day 1,3 and 5 and etoposide 70 mg/m2 IV on days 1 to 5 were administered every 3-4 wks. Filgrastim was given subcutaneouosly everyday from day 6 until the full leukocyte recovery. 25 pts. were entered and 22 pts. (8 LD, 14 ED) were eligible. Median age was 78 (range: 70-82) and PS was O/l in 16 pts. The most common toxicities were hematological. Ten (45%) and seven (32%) pts. experienced G3/4 neutropenia and thrombocytopenia, respectively. Non-hematological toxicities were mild. One patient died of sepsis associated with neutropenia. 21 pts. were evaluable for response. 17 objective responses (7 LD, 10 ED) including 5 CR (3 LD, 2 ED) were observed. The overall response rate was 81% (95%CI: 58-95%) and the CR rate was 24% (8-47%). The response rates of LD and ED were 88% (47-100%) and 77% (54-95%) respectively. The median progression free survival was 5.7 months (M) (LD 7.3 M, ED 5.7 M). The median overall survival was 9.8 M (LD 11.2 M, ED 8.7 M). We concluded this regimen is feasible for elderly SCLC.
12081 Neoadjuvant chemotherapy ifosfamide etoposide and cisplatin (VIP) in 50 patients with non small cell lung cancer (NSCLC) D. Roux ‘, M. Taiar’, J.O. Bay’, F. Kwiatkowski ‘, G. Escande”, E. Bardet 3, P. Verrelle ‘. ’ Centre J. Perrin, Clermont-Ferrand; 2C.H.U. G. Montpied, Clermont-Fenand; 3Centre 13. Gauducheau, Nantes, France From February 1990 to April 1996, we treated 50 locally advanced (MO) or metastatic (Ml) NSCLC patients (pts) with the same regimen as a neoadjuvant or induction chemotherapy. The treatment consisted in etoposide (75 ms/ms), cisplatinum (25 mg/m2) and ifosfamide (1.5 g/m’). These drugs were administered IV from day 1 to day 4 (dl to d28) for 2 courses or more (mean: 3 courses/patient). 46 pts received at least 2 courses. For all evaluable pts, the intrathoracic response was evaluated after 2 courses, only the MO responders had a third course prior to local treatment (radiation therapy or surgery). The median follow up is 21 months, Pretreatment Patient Characteristics: 44 male/6 female; mean age: 59 years; WHO performance status O-l: 33, 2-3: 17; 1 stage II, 11 stage IIIA, 15 stage 1118, 23 stage IV; 31 squamous cell, 9 adenocarcinoma, 6 indifferenciated and 4 large cell carcinoma. Toxicity: 8 of the 149 delivered courses led to grade Ill or IV hematologic toxicity. 1 patient died because of a pulmonary infection during aplasia. We never used hematopoietic growth factors. Results: 4/50 pts died early, 3 of them because of a disease progression and 1 because of toxicity. 44/46 were’evaluable with one complete response and 25 partial response (overall response: 59%). 26 MO pts were evaluable and we observed 15 responses (58%); 18 Ml pts were evaluable, 11 were responders (61%) but the high number of Tl-T2 in Ml pts explains the good thoracic response. 9 pts had surgery (4 stage IIIA, 3 stage IIIB and 2 stage IV with brain metastasis). 2 of them died right after. Survival: the median survival rate is 11 months forthe 50 pts, 14 months for the 27 MO pts, 6.5 months for the 23 Ml pts. The overall survival is 48% at 1 year and 30% at 2 years. For MO pts, 66.5% at 1 year, 42.4% at 2 years; for Ml pts 26.1% at 1 year, 13.9% at 2 years. Regarding the most important prognosis factors we observed that survival was significantly correlated with response rate, performance status and more strongly to the first one. Conclusion: VIP regimen is well tolerated with an interesting thoracic response rate in our population of non selected pts with advanced NSCLC. Randomised studies should be needed to compare the VIP efficacy to that of the other neoadjuvant treatment modalities without omitting quality of life evaluation.