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216 Second-line treatment regimen in patients with limited small cell lung cancer (SCLC)
56 12131 Phase II study of vinorelbine in elderly patients with stage Ill&IV non small cell lung cancer C. Gridelli I, F. Perrone, F. De Marinis, G. lanniello, S. Cigolari, S. Cariello, F. Di Costanzo, M. D’Aprile, A. Rossi, M. Pergola, AR. Bianco. ’ Divisione di Oncologia Medica 6, lstituto Nazionale Tumori, Nap&, Italy Lung cancer arises in 3C-35% of patients (pts) older than 70 years. In advanced non small-cell lung cancer (NSCLC) the choice of the treatment in this subset of pts is controversial. They are usually excluded from trials and considered inelegible for aggressive chemotherapy. Vinorelbine (VNR) is a new semisynthetic vinca-alkaloid active and well tolerated in advanced NSCLC with 15-29% of obiective responses (OR). It can be considered in NSCLC elderly pts. From.October 1994 to October 1995 we conducted a phase II study in stage IIIB-IV NSCLC elderly (>70 years) pts, enrolling 43 cases, according to a two-stage phase II design. The planned treatment consisted of 12 weekly administrations of VNR (30 mg/m2, i.v.). The characteristics of the pts are: males/females = 38/5; median age 73 years (range 71-80); stage IIIB/IV = 19/24; epidermoid/adenok/large-cell = 31/l l/i; ECOG PS O/1/2 = 4/l 7/22. All patients are evaluable. We observed an improvement of PS and symptoms in 25% and 44% of pts, respectively. Main toxicities were (% of pts): grade 3/4 leukopenia = 23.3%/9.3%, grade 3 thrombocytopenia = 2.3%, grade 2/3 anoemia = 16.3%/2.3%, grade 22 fatigue 11.7%, grade 2 neurotoxicity 7.0%. Median delivered dose-intensity was 21.4 mg/m2week. We reported 10 partial responses: (OR 23.3%; exact 95% confidence limits 11.8%38.6%). l-year estimated progression-free and overall survival are 20% and 38%, respectively. Estimated median survival is 37 weeks. In advanced NSCLC elderly pts VNR was well tolerated and active. Suggested schedule for further studies is 30 mg/m’ day 1, 8 recycling every 3 weeks. A phase III randomized trial of supportive care (SC) vs SC+VNR, with quality of life as primary end-point, is ongoing.
I214
Early phase II trials of biochemical modulation therapy for small cell lung cancer (SCLC)
K. Yanagihara, Y. Otake, F. Tanaka, of Thoracic Surgery, Chest Disease Kyoto, Japan
(BCM)
T. Fukuse, S. Hitomi, H. Wada. Dept Research Institute, Kyoto Univ.,
In general, the first choice of chemotherapy for SCLC is combination of VP-16 and cisplatin (EP therapy), but because of its severe adverse effects EP therapy may be not suitable for such as patients with renal disfunction and/or poor performance status. We successfully treated patients with non-small cell lung cancer (NSCLC) by BCM therapy without severe adverse effects, and recently we designed early Phase II trials to use 5-fluorouracil (5-FU) which is characterized as a time-dependent drug. BCM therapy in our trial consists of cisplatin as a modulator and 5-FU and UFT as effecters. According to our protocol for NSCLC we designed a trial to SCLC. The early phase II trial for untreated patients with SCLC is as follows: Cisplatin
6 mgldlday
5-FU
150 mglm2iday
UFT
300 mg/day (body weight ~50 kg) or 400 mg/day (body weight ~50 kg)
intravenous drip infusion intravenous continuous infusion oral oral
day 1-5 day l-7 every day every day
This cycle of chemotherapy is administered every week. Median treatment course was four cycles for total ten patients. Six partial responses (60%) and four no changes (40%) were obtained. A Grade 3 neutrocytopaenia was observed in three patients (30%) and a Grade 3 thrombocytopaenia in two patients. A Grade 3 vomiting was observed in one patient and a Grade 3 diarrhea in one patient. In no cases Grade 2-3 renal injury was observed. In six limited disease cases one patient died eight months after BCM therapy. The remaining 5 patients survived for more than one year. In four extensive disease cases all patients died and a median survival time was six months after BCM therapy. This BCM therapy may be one of useful chemotherapy in cases with various complications.
12151 Gemcitabine, ifosfamide and cisplatin (GIP) in the treatment of advanced non-small cell lung cancer. A phase II trial C. Vadell, J. Carles, M. Gallen, R. Ibeas, I. Tusquets, A. Miguel, K. Villadiego, X. Fabregat. Medical Oncology Service, Hospital Universitari de/ Mar, Barcelona, Spain This phase II trial was established to assess the activity of Gemcitabine (G) in combination with lfosfamide (I) and Cisplatin (P) in patients with advanced non-small cell lung cancer. G was given at dose of 1000 mg/m2 days 1 and 8, I at dose of 3 gr/m2 day 1 and P at dose of 50 mg/m2, all on day 1 of a 21 day cycle. Since march 1996 to november 1996, 18 patients have been enrolled, all evaluable for toxicity and 14 evaluable for response. Patient characteristics were: 17 men and 1 women, mean age of 64 years (41-75). One patient was staged as IIIA, 12 as IIIB and 5 as IV. The total number of cycles administered is 69. G dose has been reduced in 34 cycles (12 patients) and I in 4 cycles (1 patient). The average dose administered over dose planned was 71.5% for G, 98% for I and 100% for P. Toxicity registered (WHO grades III/IV) was: Alopecia = 7/O, Gastrointestinal = l/O, Haemoglobin = 2/O, Leucocytes = 6/O, Neutrophils = 7/l, Platelets = l/O. One episode of neutropenic fever occurred, without documented infection. There were not treatment related deaths. Fourteen patients are evaluable for response, and we have assessed 6 partial response, 2 stable disease and 6 progression. Conclusions: GIP chemotherapy is an active regimen in advanced non-small cell lung cancer, with an acceptable toxicity. This abstract shows preliminary results, that should be confirmed after finishing the previst recruitment of 40 patients.
I216
Second-line treatment regimen in patients with limited small cell lung cancer (SCLC)
N.F. Orel, V.A. Gorbunova, Cent., Moscow, Russia
M.B. Bychkov,
N.B. Smirnova.
Can. Res.
In contrast to the other types of lung cancer, SCLC is highly sensitive to both chemotherapy and radiotherapy. After initial chemotherapy SCLC become refractory to future treatment and is often incurable. In this cases in majority of studies is using non-cross resistant combination chemotherapy. In 101 pts with limited SCLC were studied 9 chemotherapy regimen as second-line treatment after antracycline-based regimen. Results: 1. VPP (VP+ DDP)-7pts, RR-42.9%, CR-28.6%, PR-14.3%; II. VIP (VP + I + DDP) - 11 pts, RR-36.4%, CR-18.2%, PR-18.2%; Ill. Ifosfamide (I) - 10 pts, RR-30%, CR-lo%, PR - 20%; IV. Aranoza (new russian nitrosomethylurea compound) + Cycloplatam (new russian platinum containing compounds) - 8 pts, RR-25%, PR-25%; V. IP (I+DDP) 11 pts, RR-22%, CR - ll%, PR - 11%; VI. NMU + DDP + VCR - 16 pts, RR-18.8%, PR-18.8%; VII. NMU + Platin (new russian platinum containing compounds) + VCR -20 pts, RR-lo%, PR-10%; VIII. Vepeside per OS (VP) - 14 pts-21.4% stabilisation; XI. CEMV (Cyc + Farm + MTX + VCR) - 4 pts, 4 stabilisation; Conclusion: Platinum compounds containing regimen are effective after antracycline-based regimen. Most promising seems VIP and VPP combinations as a second-line treatment of SCLC, also after intensive chemotherapy with GM-CSF.
I217
A randomised, concentration-controlled, comparison of standard (5 day) vs prolonged (15 day) infusions of etoposide phosphate in small cell lung cancer (SCLC)
S. Joel ’ , K. O’Byrne 2, R. Penson ‘, D. Papamichael ‘, A. Higgins ’ , H. Robertshaw, R. Rudd ‘, D. Talbot2, M. Slevin ‘. ’ /CRF Departments Medical Oncology, St Bartholomew’s Hospital, London; 2 Churchill Hospital, Oxford, UK
of
Recent reports have described the activity of prolonged infusional etoposide in SCLC. This randomised trial was designed to investigate the activity and toxicity of continuous infusion etoposide phosphate (EP), targeting a plasma etoposide concentration of either 3 &ml for 5 days (5 d) or 1 &ml for 15 days (15 d) in previously untreated, extensive disease, SCLC patients. EP was used as a single agent. Plasma etoposide concentration was monitored on days 2 and 4 in pts receiving 5d EP and on days 2,
I214
Early phase II trials of biochemical modulation therapy for small cell lung cancer (SCLC)
K. Yanagihara, Y. Otake, F. Tanaka, of Thoracic Surgery, Chest Disease Kyoto, Japan
(BCM)
T. Fukuse, S. Hitomi, H. Wada. Dept Research Institute, Kyoto Univ.,
In general, the first choice of chemotherapy for SCLC is combination of VP-16 and cisplatin (EP therapy), but because of its severe adverse effects EP therapy may be not suitable for such as patients with renal disfunction and/or poor performance status. We successfully treated patients with non-small cell lung cancer (NSCLC) by BCM therapy without severe adverse effects, and recently we designed early Phase II trials to use 5-fluorouracil (5-FU) which is characterized as a time-dependent drug. BCM therapy in our trial consists of cisplatin as a modulator and 5-FU and UFT as effecters. According to our protocol for NSCLC we designed a trial to SCLC. The early phase II trial for untreated patients with SCLC is as follows: Cisplatin
6 mgldlday
5-FU
150 mglm2iday
UFT
300 mg/day (body weight ~50 kg) or 400 mg/day (body weight ~50 kg)
intravenous drip infusion intravenous continuous infusion oral oral
day 1-5 day l-7 every day every day
This cycle of chemotherapy is administered every week. Median treatment course was four cycles for total ten patients. Six partial responses (60%) and four no changes (40%) were obtained. A Grade 3 neutrocytopaenia was observed in three patients (30%) and a Grade 3 thrombocytopaenia in two patients. A Grade 3 vomiting was observed in one patient and a Grade 3 diarrhea in one patient. In no cases Grade 2-3 renal injury was observed. In six limited disease cases one patient died eight months after BCM therapy. The remaining 5 patients survived for more than one year. In four extensive disease cases all patients died and a median survival time was six months after BCM therapy. This BCM therapy may be one of useful chemotherapy in cases with various complications.
12151 Gemcitabine, ifosfamide and cisplatin (GIP) in the treatment of advanced non-small cell lung cancer. A phase II trial C. Vadell, J. Carles, M. Gallen, R. Ibeas, I. Tusquets, A. Miguel, K. Villadiego, X. Fabregat. Medical Oncology Service, Hospital Universitari de/ Mar, Barcelona, Spain This phase II trial was established to assess the activity of Gemcitabine (G) in combination with lfosfamide (I) and Cisplatin (P) in patients with advanced non-small cell lung cancer. G was given at dose of 1000 mg/m2 days 1 and 8, I at dose of 3 gr/m2 day 1 and P at dose of 50 mg/m2, all on day 1 of a 21 day cycle. Since march 1996 to november 1996, 18 patients have been enrolled, all evaluable for toxicity and 14 evaluable for response. Patient characteristics were: 17 men and 1 women, mean age of 64 years (41-75). One patient was staged as IIIA, 12 as IIIB and 5 as IV. The total number of cycles administered is 69. G dose has been reduced in 34 cycles (12 patients) and I in 4 cycles (1 patient). The average dose administered over dose planned was 71.5% for G, 98% for I and 100% for P. Toxicity registered (WHO grades III/IV) was: Alopecia = 7/O, Gastrointestinal = l/O, Haemoglobin = 2/O, Leucocytes = 6/O, Neutrophils = 7/l, Platelets = l/O. One episode of neutropenic fever occurred, without documented infection. There were not treatment related deaths. Fourteen patients are evaluable for response, and we have assessed 6 partial response, 2 stable disease and 6 progression. Conclusions: GIP chemotherapy is an active regimen in advanced non-small cell lung cancer, with an acceptable toxicity. This abstract shows preliminary results, that should be confirmed after finishing the previst recruitment of 40 patients.
I216
Second-line treatment regimen in patients with limited small cell lung cancer (SCLC)
N.F. Orel, V.A. Gorbunova, Cent., Moscow, Russia
M.B. Bychkov,
N.B. Smirnova.
Can. Res.
In contrast to the other types of lung cancer, SCLC is highly sensitive to both chemotherapy and radiotherapy. After initial chemotherapy SCLC become refractory to future treatment and is often incurable. In this cases in majority of studies is using non-cross resistant combination chemotherapy. In 101 pts with limited SCLC were studied 9 chemotherapy regimen as second-line treatment after antracycline-based regimen. Results: 1. VPP (VP+ DDP)-7pts, RR-42.9%, CR-28.6%, PR-14.3%; II. VIP (VP + I + DDP) - 11 pts, RR-36.4%, CR-18.2%, PR-18.2%; Ill. Ifosfamide (I) - 10 pts, RR-30%, CR-lo%, PR - 20%; IV. Aranoza (new russian nitrosomethylurea compound) + Cycloplatam (new russian platinum containing compounds) - 8 pts, RR-25%, PR-25%; V. IP (I+DDP) 11 pts, RR-22%, CR - ll%, PR - 11%; VI. NMU + DDP + VCR - 16 pts, RR-18.8%, PR-18.8%; VII. NMU + Platin (new russian platinum containing compounds) + VCR -20 pts, RR-lo%, PR-10%; VIII. Vepeside per OS (VP) - 14 pts-21.4% stabilisation; XI. CEMV (Cyc + Farm + MTX + VCR) - 4 pts, 4 stabilisation; Conclusion: Platinum compounds containing regimen are effective after antracycline-based regimen. Most promising seems VIP and VPP combinations as a second-line treatment of SCLC, also after intensive chemotherapy with GM-CSF.
I217
A randomised, concentration-controlled, comparison of standard (5 day) vs prolonged (15 day) infusions of etoposide phosphate in small cell lung cancer (SCLC)
S. Joel ’ , K. O’Byrne 2, R. Penson ‘, D. Papamichael ‘, A. Higgins ’ , H. Robertshaw, R. Rudd ‘, D. Talbot2, M. Slevin ‘. ’ /CRF Departments Medical Oncology, St Bartholomew’s Hospital, London; 2 Churchill Hospital, Oxford, UK
of
Recent reports have described the activity of prolonged infusional etoposide in SCLC. This randomised trial was designed to investigate the activity and toxicity of continuous infusion etoposide phosphate (EP), targeting a plasma etoposide concentration of either 3 &ml for 5 days (5 d) or 1 &ml for 15 days (15 d) in previously untreated, extensive disease, SCLC patients. EP was used as a single agent. Plasma etoposide concentration was monitored on days 2 and 4 in pts receiving 5d EP and on days 2,