- Email: [email protected]
Phase I study of weekly cisplatin (C) and docetaxel (D) in patients with inoperable non-small cell lung cancer (NSCLC)
78
•2--•
Chemotherapy Chemotherapy and its pharmacokinetics (PK) study during maintenance hemodialysis in patients with primary lung cancer and renal failure
R. Watanabe, Y. Takiguchi, T. Moriya, H. Kimura, S. Masuyama, S. Oda, K. Nagao, T. Kuriyama. Department of Chest medicine, Chiba
University School of Medicine, Chiba; Division of blood purification, Chiba University School of Medicine, Chiba; Health sciences center, Chiba University, Chiba, Japan Purpose: To elucidate feasibility of chemotherapy for patients with primary lung cancer and renal failure that require maintenance hemodialysis, PK studies of cisplatin and etoposide were performed in three patients in this situation. Patients and Methods: Chemotherapeutic agents consisting of cisplatin at day 1, and etoposide at day 1, 3, and 5 were administered. A regular hemodialysis utilizing a high performance membrane was started at 30 min after the completion of each administration at day 1, 3, and 5. By monitoring PK data and toxic reactions, doses of the drugs were gradually escalated. The doses of cisplatin and etoposide in mg/m2 were as follows: 40 and 50 for the 1st, 80 and 50 for the 2nd courses of Case 1; 40 and 100 for the 1 st, 80 and 100 for the 2 nd courses of Case 2, respectively. Finally, four courses of the full dose chemotherapy consisting of 80 mg/m2 cisplatin and 100 mg/m2 etoposide were administered to Case 3. Results: The PK parameters of total platinum (t-Pt), free platinum (f-Pt), and etoposide showed similar patterns to those obtained from other patients with normal renal function, except for minor differences. Higher concentrations than detection limit (25 ng/ml) of the f-Pt in those three patients, however, were maintained for two weeks, whereas those were maintained for only three hours in a patient with normal renal function. Although all three patients experienced grade 2 or 3 leukocytopenia, thrombocytopenia, or anemia, all of them were completely recovered. No other major toxicity was observed. Conclusion: The data suggest that the standard dose combination chemotherapy consisting of cisplatin and etoposide is feasible even for cancer patients with renal failure that requires hemodialysis, when monitored by PK study.
I•']
second high dose cycle because of toxicity. Despite higher doses of cisplatin, no renal toxicity was observed with amifostine.
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Vinorelbine, ifosfamide and cisplatin in non-small cell lung cancer E.H. Tan. Department of Medical Oncology, National Cancer Centre, Singapore
The combination of vinorelbine, ifosfamide and cisplatin (NIP) was used in non-small cell lung cancer (NSCLC) in Singapore since 1994. Between Sept 1994 and July 1997, a total of 76 patients (pts) with stage IliB/IV/recurrent metastatic NSCLC were treated with NIP at the following doses: vinorelbine 25 mg/m2 on days 1 and 8, ifosfamide 3 gm/m 2 on day 1 with MESNA at 60% of the ifosfamide dose for uroprotection, and cisplatin 50 mg/m 2 on day 1. The cycle was repeated every 21 days. An overall response rate of 58% was attained (1% complete response). The median survival was 14 months (mths) and the 1-yr survival rate was 60%. Given the encouraging results with this combination, we proceeded to use this regimen in locally advanced (stage IlIA/B) as combined modality with thoracic radiotherapy (TRT). The treatment schedule was as follows: 2 cycles of NIP followed by thoracic radiotherapy of 64 Gy from week 7 with daily cispiatin at 6 mg/m2 as radiosensitiser and 2 further cycles of adjuvant NIP after completion of radiation. Forty-four pts were treated this way. Overall response to induction treatment was 75% (2 complete responders). Six pts achieved complete responses after completion of TRT. At median followup of 35 mths, the median survival for stage IliA pts was 19 mths with 3-yr survival of 39%. In contrast, the median survival of stage IIIB pts was only 13 mths and only 15% were alive at 3 yrs. The updated results of the latter study will be presented at the meeting.
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Phase I study of weekly cisplatin (C) and docetaxel (D) in patients with inoperable non-small cell lung cancer (NSCLC)
T. Yana, M. Takada, S. Sakai, S. Tsukiyama, K. Higuchi, B. Kishino, K. Nakagawa, N. Yamamoto, M. Fukuoka. Rinku General Medical
Center, Izumisano; Kinki University Medical School, Osakasayama, Japan Phase II trial of high dose chemotherapy with amifostine and concurrent irradiation in limited disease small cell lung cancer (SCLC)
L, Falchero, P. Foumel, I. Court-Fortune, S. Hominal, P. Rebattu, P.J. Souquet, M. Perol, H. Janicot, R. Riou, X. Tchenio, C. Marichy.
Groupe Lyon, St Etienne Oncologie Thoracique (CLOT); Centre Hospitalier Villefranche Sur SaOne, France Dose intensification of initial chemotherapy in appropriate patients with limited SCLC has been associated with statistically significant improvement in survival. We conducted a multicentric prospective study to examine the feasibility of higher doses of cisplatin (P) (80 mg/m2 days 1 and 5), etoposide (V) (80 mg/m2/d days 1-5) with amifostine (740 mg/m2 days 1 and 5) with G-CSF on the first and fourth courses of chemotherapy. Thoracic irradiation to 60 Gy (30 fractions) was administred concurrently to the second and third courses of standard chemotherapy (P-80 mg/m 2 day 1; V-80 mg/m2/d days 1-3). Prophylactic cranial irradiation (24 Gy-12 fractions) was administred 4 weeks after the fourth course of chemotherapy in case of complete response (CR). 24 patients (pts) (20 male, 4 female), median age 55 years (39-69), ECOG PS 0-1 were enrolled. At present, 18 pts are evaluable for adverse reaction and response. Twelve pts completed the overall treatment. Two pts (11%) died prior to treatment completion because of febrile neutropenia. OMS grade Ill/IV toxicity % of courses: neutropenia cycle 1-28%, cycle 11-13%, cycle 111-53%, cycle IV-42%, anemia 11%, thrombocytopenia 25%, vomiting 25%, mucositis 7%, peripheral neuropathy 3%, hypotension 3%. No other grade Ill/IV toxicity was observed. Clinical response (12 pts): overall response 67% with CR 50%, PR 17%, SD 17%, PD 16%. In conclusion this regimen is efficacious but only 66% of pts were able to receive the
We conducted a phase I study to determine the maximum tolerated dose (MTD) of weekly C and D in chemonaive patients (pts) with inoperable NSCLC and to define dose-limiting toxicities (DLTs). ELIGIBILITY: Stage III or IV NSCLC, PS 0-1, chemonaive, and adequate organ functions. TREATMENT SCHEDULE: Pts were treated with D on days 1, 8, and 15 of a 28-day cycle in combination with concurrent C 25 mg/m2. The starting dose of D was 20 mg/m 2, and the D dose was escalated in 5-mg/m 2 increments. DLT was defined as grade (G) 4 neutropenia (N) lasting [>] 4 days, G4 thrombocytopenia (T) _>4 days or associated with a bleeding episode or requiring platelet transfusion, or nonhematologic grade 3 or 4 toxicity with the exception of alopecia, nausea and vomiting. The MTD was determined when greater than one third of patients experienced acute DLT at a given dose. Results: Twenty-two pts were enrolled on this study [14 male/8 female, median age 63 (range, 43-75), 5 IIIN10 IIIB/7 IV, 15 Ad/5 Sq/2 La]. All had PS 1. Dose escalation and toxicities were shown below: Level
D
Pts
G4 N & T G 3-4 Nonhem
DLT
1 2 3 4 5 6
20 25 30 35 40 45
3 6 3 3 6 1
0 0 0 0 0 0
0 0 0 0 0 1
0 0 0 0 0 1
Chemotherapy Dose escalation was finished at the level of 6. Neurotoxicity is the DLT of this weekly C-D combination regimen. The MTD is D 45 mg/m 2 days 1, 8, and 15 combined concurrent C 25 mg/m2 of a 28-day cycle. Conclusion: The recommended dose is 40 mg/m 2 docetaxel of this regimen. We are planning to the phase II study.
[•7•
Treatment of advanced non-small-cell lung cancer failed to paclitaxel based therapy - Is Docetaxel (Taxotere*) useful?
R. Kumar. Medical Oncologist, Apollo Hospital Jubilee Hills, Hyderabad, India Objective: To evaluate the efficacy of Docetaxel (Taxotere *) with Carboplatin in patients (pts.) with advanced Non-small-ceil Lung Cancer (NSCLC) who have been previously treated with Paclitaxel based regimen, and who have failed to respond, or subsequently relapsed after therapy. Introduction: Systemic chemotherapy for pts. with advanced NSCLC, in good performance status, has resulted in prolonged survival and improved quality of life through better symptom control. Newer agents have shown more promise, notably the taxanes, especially in the second-line treatment of platinum-based protocol failures. The efficacy of Docetaxel in Paclitaxel failed patients has not been sufficiently studied, especially in the Indian sub-continent. Patients & Methods: Four pts. with histologically proven NSCLC, in advanced stage (Stages Ill & IV) who have either failed to respond or relapsed after treatment with Paclitaxel based regimen, have been included till now in this prospective study. Pts. are in the age group of 55 to 70 years (median age 61.7 years) with a performance stares of >70% (Karnofsky scale) and with a >16 weeks expected survival. Pts. with significant hepatic, renal, cardiac or pulmonary dysfunction were excluded. Treatment protocol consisted of Docetaxel (Taxotere *) 80 mg/m2, i.v. infusion over 1 hour, (day-l) and Carboplatin 450 mg/m2, i.v. infusion (day-2), with dexamethasone, ondansetron, and ranitidine as premedication, repeated every 3 weeks. All patients received GCSF (Granocyte *) on days 3 to 6, every course. Tumor response was assessed by clinical examination, chest X-ray, and CT-Scan. Quality-oflife was evaluated by a questionnaire. The median number of courses given per pt. were three. The median follow-up has been 4.5 months. A total of 6 courses, progression of disease, unacceptable toxicity or death of the patient would be the end-point of the study. Results: As this is an ongoing study, the results presented are interim. Three pts. have achieved partial response (PR) and one experienced disease progression. No complete responses have been observed till now. Quality-of-life improvement was significant. Toxicity observed was neutropenia, rash, alopecia, diarrhoea, and fluid retention. The median duration of response has been 4.2 months over a median followup of 4.5 months. Conclusions: Docetaxel (Taxotere *), in combination with Carboplatin, seems to be of premise in the treatment of advanced NSCLC, even in pts. who have failed to respond or relapsed after Paclitaxel based therapy, with acceptable toxicity. Comment: This is an ongoing prospective study with continuing recruitment, and hence this data is interim. Complete and updated manuscript would be presented in the conference * TM of Rhone-Poulenc Ltd.
•8•
CisplaUn-gemcitabine, vs. cisplatin-gemcitabinevinorelbine, vs. cisplaUn-gemcitabine-paclitaxel in advanced non-small-cell lung cancer. First-stage analysis of a Southern Italy Cooperative Oncology Group (SlCOG) phase III trial
P. Comella, G. Frasci, N. Panza, G. Nicolella, L. Manzione, G. De Cataldis, R. Cioffi, E. Micillo, V. Lorusso, D. Bilancia, L. Maiorino, F.V. Piantedosi, A. Mangiameli, A. Gravina, A. Lamberti, M. De Lena, G. Cornelia. For the Southern Italy Cooperative Oncology Group
79
suits in advanced non-small cell lung cancer (NSCLC) patients. The present study aimed at comparing the PGV and PGT regimens with the cisplatin-gemcitabine (PG) combination. Patients and Methods: From October 1997, patients with locally advanced or metastatic disease NSCLC, aged <70 years and with ECOG PS _< 1, randomly received: cisplatin 50 mg/m2 + gemcitabine 1,000 mg/m 2 + vinorelbine 25 mg/m2 d 1 & 8 q 3 wk (PGV); cisplatin 100 mg/m 2 d 1 + gemcitabine 1,000 mg/m 2 d 1, 8, 15 q 4 wk (PG); cisplatin 50 mg/m2 + gemcitabine 1,000 mg/m2 + paclitaxe1125 mg/m 2 d 1 & 8 q 3 wk (PGT). Survival was the primary end-point of the study, and a final sample size of 120 patients per arm was set. An interim survival analysis was planned after the enroiment of 60 pts. Results: Until Sept. 30 1999, 247 patients (PG = 82, PGV = 84, PGT -- 81) had been enrolled (stage IIIB, 93; stage IV, 154). At that time the survival data of the first 60 pts. in each arm who had a >12week follow-up were analysed by an independent monitoring board. At an 11-month median follow-up 103 deaths have occurred, and the MST for the entire population is 48 weeks. The observed differences in survival between the 3 arms did not meet the criteria for the early stopping of the study. Conclusions: The accrual still continues. We expect to reach the final sample size within December '99, and to perform the final analysis in April 2000.
~ - - ~ Multi-center study with paclitaxel (P)lcarboplatin (C) in advanced or metastatic non-small cell lung cancer (NSGLC) patients (pts) P. Glorieux 1, P. Ortmanns 2, S. Marien 3, R. Degives4, D. Degraeve5, M. Potvin6, D. Grauwels 7, D. SchaUier7. 1Clin. Sud Luxembourg,
At/on; 2H. Fami/ie, Rumst; 3H. Hart, Lier; 4Bois de/'Abbaye, Seraing; 5St. Franciskus, Heusden-Zo/der; 6Van Enschodt, Boom; 7Bristo/_Myers Squibb, Belgium Purpose: To evaluate the efficacy and toxicity of paclitaxel (TAXOL®) at two different dose levels and carboplatin (PARAPLATIN®) for the treatment of chemonaive NSCLC patients stage IIIA-B and IV in a large multi-center setting. To evaluate the feasibility of carboplatin dosing via the Chatelut formula. Pts and Methods: Histologically documented NSCLC pts with measurable disease, an ECOG PS = 0-2. Treatment consisted of an every 3 weeks administration of P either at 175 mg/m_ or 200 mg/m_ by 3-hour IV infusion followed by C at an area under the concentration/time curve (AUC) = 6 using the Chatelut formula. Results: 144 pts were enrolled and data of 118 pts were available for this analysis:
N° pts median age (years) male/female Stage IIINIIIB/IV Histology SCC/ADC/LC/other Response (%) Time to progression (months) Median survival (months) One year survival Toxicity (NCIC CTC Gr 3-4) - Neutropenia - Thrombocytopenia - Neurotoxicity - Myalgia/arthrslgia - Febrile neutropenia
PC 200/6
PC 175/6
97 63.7 82/15 5139153
21 66.1 19/2 1/5/15
38/24/13•22 21/80 (27.5%) 4.3 8.8 36%
8/7/3/3 4/19 (21.0%) 3.7 6.7 32%
59% 14.5% 13% 7% 7%
48% 19% 5% 5% 5%
(S/COG); clo Tumor Institute of Naples, Italy Purpose: Both the cisplatin-gemcitabine-vinorelbine (PGV) and the cisplatin-gemcitabine-paclitaxel (PGT) regimens gave promising re-
Conclusion: This large multi-center study confirms the efficacy and safety of PC as first line treatment of stage IlIA-B/IV NSCLC at both
•2--•
Chemotherapy Chemotherapy and its pharmacokinetics (PK) study during maintenance hemodialysis in patients with primary lung cancer and renal failure
R. Watanabe, Y. Takiguchi, T. Moriya, H. Kimura, S. Masuyama, S. Oda, K. Nagao, T. Kuriyama. Department of Chest medicine, Chiba
University School of Medicine, Chiba; Division of blood purification, Chiba University School of Medicine, Chiba; Health sciences center, Chiba University, Chiba, Japan Purpose: To elucidate feasibility of chemotherapy for patients with primary lung cancer and renal failure that require maintenance hemodialysis, PK studies of cisplatin and etoposide were performed in three patients in this situation. Patients and Methods: Chemotherapeutic agents consisting of cisplatin at day 1, and etoposide at day 1, 3, and 5 were administered. A regular hemodialysis utilizing a high performance membrane was started at 30 min after the completion of each administration at day 1, 3, and 5. By monitoring PK data and toxic reactions, doses of the drugs were gradually escalated. The doses of cisplatin and etoposide in mg/m2 were as follows: 40 and 50 for the 1st, 80 and 50 for the 2nd courses of Case 1; 40 and 100 for the 1 st, 80 and 100 for the 2 nd courses of Case 2, respectively. Finally, four courses of the full dose chemotherapy consisting of 80 mg/m2 cisplatin and 100 mg/m2 etoposide were administered to Case 3. Results: The PK parameters of total platinum (t-Pt), free platinum (f-Pt), and etoposide showed similar patterns to those obtained from other patients with normal renal function, except for minor differences. Higher concentrations than detection limit (25 ng/ml) of the f-Pt in those three patients, however, were maintained for two weeks, whereas those were maintained for only three hours in a patient with normal renal function. Although all three patients experienced grade 2 or 3 leukocytopenia, thrombocytopenia, or anemia, all of them were completely recovered. No other major toxicity was observed. Conclusion: The data suggest that the standard dose combination chemotherapy consisting of cisplatin and etoposide is feasible even for cancer patients with renal failure that requires hemodialysis, when monitored by PK study.
I•']
second high dose cycle because of toxicity. Despite higher doses of cisplatin, no renal toxicity was observed with amifostine.
~-]
Vinorelbine, ifosfamide and cisplatin in non-small cell lung cancer E.H. Tan. Department of Medical Oncology, National Cancer Centre, Singapore
The combination of vinorelbine, ifosfamide and cisplatin (NIP) was used in non-small cell lung cancer (NSCLC) in Singapore since 1994. Between Sept 1994 and July 1997, a total of 76 patients (pts) with stage IliB/IV/recurrent metastatic NSCLC were treated with NIP at the following doses: vinorelbine 25 mg/m2 on days 1 and 8, ifosfamide 3 gm/m 2 on day 1 with MESNA at 60% of the ifosfamide dose for uroprotection, and cisplatin 50 mg/m 2 on day 1. The cycle was repeated every 21 days. An overall response rate of 58% was attained (1% complete response). The median survival was 14 months (mths) and the 1-yr survival rate was 60%. Given the encouraging results with this combination, we proceeded to use this regimen in locally advanced (stage IlIA/B) as combined modality with thoracic radiotherapy (TRT). The treatment schedule was as follows: 2 cycles of NIP followed by thoracic radiotherapy of 64 Gy from week 7 with daily cispiatin at 6 mg/m2 as radiosensitiser and 2 further cycles of adjuvant NIP after completion of radiation. Forty-four pts were treated this way. Overall response to induction treatment was 75% (2 complete responders). Six pts achieved complete responses after completion of TRT. At median followup of 35 mths, the median survival for stage IliA pts was 19 mths with 3-yr survival of 39%. In contrast, the median survival of stage IIIB pts was only 13 mths and only 15% were alive at 3 yrs. The updated results of the latter study will be presented at the meeting.
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Phase I study of weekly cisplatin (C) and docetaxel (D) in patients with inoperable non-small cell lung cancer (NSCLC)
T. Yana, M. Takada, S. Sakai, S. Tsukiyama, K. Higuchi, B. Kishino, K. Nakagawa, N. Yamamoto, M. Fukuoka. Rinku General Medical
Center, Izumisano; Kinki University Medical School, Osakasayama, Japan Phase II trial of high dose chemotherapy with amifostine and concurrent irradiation in limited disease small cell lung cancer (SCLC)
L, Falchero, P. Foumel, I. Court-Fortune, S. Hominal, P. Rebattu, P.J. Souquet, M. Perol, H. Janicot, R. Riou, X. Tchenio, C. Marichy.
Groupe Lyon, St Etienne Oncologie Thoracique (CLOT); Centre Hospitalier Villefranche Sur SaOne, France Dose intensification of initial chemotherapy in appropriate patients with limited SCLC has been associated with statistically significant improvement in survival. We conducted a multicentric prospective study to examine the feasibility of higher doses of cisplatin (P) (80 mg/m2 days 1 and 5), etoposide (V) (80 mg/m2/d days 1-5) with amifostine (740 mg/m2 days 1 and 5) with G-CSF on the first and fourth courses of chemotherapy. Thoracic irradiation to 60 Gy (30 fractions) was administred concurrently to the second and third courses of standard chemotherapy (P-80 mg/m 2 day 1; V-80 mg/m2/d days 1-3). Prophylactic cranial irradiation (24 Gy-12 fractions) was administred 4 weeks after the fourth course of chemotherapy in case of complete response (CR). 24 patients (pts) (20 male, 4 female), median age 55 years (39-69), ECOG PS 0-1 were enrolled. At present, 18 pts are evaluable for adverse reaction and response. Twelve pts completed the overall treatment. Two pts (11%) died prior to treatment completion because of febrile neutropenia. OMS grade Ill/IV toxicity % of courses: neutropenia cycle 1-28%, cycle 11-13%, cycle 111-53%, cycle IV-42%, anemia 11%, thrombocytopenia 25%, vomiting 25%, mucositis 7%, peripheral neuropathy 3%, hypotension 3%. No other grade Ill/IV toxicity was observed. Clinical response (12 pts): overall response 67% with CR 50%, PR 17%, SD 17%, PD 16%. In conclusion this regimen is efficacious but only 66% of pts were able to receive the
We conducted a phase I study to determine the maximum tolerated dose (MTD) of weekly C and D in chemonaive patients (pts) with inoperable NSCLC and to define dose-limiting toxicities (DLTs). ELIGIBILITY: Stage III or IV NSCLC, PS 0-1, chemonaive, and adequate organ functions. TREATMENT SCHEDULE: Pts were treated with D on days 1, 8, and 15 of a 28-day cycle in combination with concurrent C 25 mg/m2. The starting dose of D was 20 mg/m 2, and the D dose was escalated in 5-mg/m 2 increments. DLT was defined as grade (G) 4 neutropenia (N) lasting [>] 4 days, G4 thrombocytopenia (T) _>4 days or associated with a bleeding episode or requiring platelet transfusion, or nonhematologic grade 3 or 4 toxicity with the exception of alopecia, nausea and vomiting. The MTD was determined when greater than one third of patients experienced acute DLT at a given dose. Results: Twenty-two pts were enrolled on this study [14 male/8 female, median age 63 (range, 43-75), 5 IIIN10 IIIB/7 IV, 15 Ad/5 Sq/2 La]. All had PS 1. Dose escalation and toxicities were shown below: Level
D
Pts
G4 N & T G 3-4 Nonhem
DLT
1 2 3 4 5 6
20 25 30 35 40 45
3 6 3 3 6 1
0 0 0 0 0 0
0 0 0 0 0 1
0 0 0 0 0 1
Chemotherapy Dose escalation was finished at the level of 6. Neurotoxicity is the DLT of this weekly C-D combination regimen. The MTD is D 45 mg/m 2 days 1, 8, and 15 combined concurrent C 25 mg/m2 of a 28-day cycle. Conclusion: The recommended dose is 40 mg/m 2 docetaxel of this regimen. We are planning to the phase II study.
[•7•
Treatment of advanced non-small-cell lung cancer failed to paclitaxel based therapy - Is Docetaxel (Taxotere*) useful?
R. Kumar. Medical Oncologist, Apollo Hospital Jubilee Hills, Hyderabad, India Objective: To evaluate the efficacy of Docetaxel (Taxotere *) with Carboplatin in patients (pts.) with advanced Non-small-ceil Lung Cancer (NSCLC) who have been previously treated with Paclitaxel based regimen, and who have failed to respond, or subsequently relapsed after therapy. Introduction: Systemic chemotherapy for pts. with advanced NSCLC, in good performance status, has resulted in prolonged survival and improved quality of life through better symptom control. Newer agents have shown more promise, notably the taxanes, especially in the second-line treatment of platinum-based protocol failures. The efficacy of Docetaxel in Paclitaxel failed patients has not been sufficiently studied, especially in the Indian sub-continent. Patients & Methods: Four pts. with histologically proven NSCLC, in advanced stage (Stages Ill & IV) who have either failed to respond or relapsed after treatment with Paclitaxel based regimen, have been included till now in this prospective study. Pts. are in the age group of 55 to 70 years (median age 61.7 years) with a performance stares of >70% (Karnofsky scale) and with a >16 weeks expected survival. Pts. with significant hepatic, renal, cardiac or pulmonary dysfunction were excluded. Treatment protocol consisted of Docetaxel (Taxotere *) 80 mg/m2, i.v. infusion over 1 hour, (day-l) and Carboplatin 450 mg/m2, i.v. infusion (day-2), with dexamethasone, ondansetron, and ranitidine as premedication, repeated every 3 weeks. All patients received GCSF (Granocyte *) on days 3 to 6, every course. Tumor response was assessed by clinical examination, chest X-ray, and CT-Scan. Quality-oflife was evaluated by a questionnaire. The median number of courses given per pt. were three. The median follow-up has been 4.5 months. A total of 6 courses, progression of disease, unacceptable toxicity or death of the patient would be the end-point of the study. Results: As this is an ongoing study, the results presented are interim. Three pts. have achieved partial response (PR) and one experienced disease progression. No complete responses have been observed till now. Quality-of-life improvement was significant. Toxicity observed was neutropenia, rash, alopecia, diarrhoea, and fluid retention. The median duration of response has been 4.2 months over a median followup of 4.5 months. Conclusions: Docetaxel (Taxotere *), in combination with Carboplatin, seems to be of premise in the treatment of advanced NSCLC, even in pts. who have failed to respond or relapsed after Paclitaxel based therapy, with acceptable toxicity. Comment: This is an ongoing prospective study with continuing recruitment, and hence this data is interim. Complete and updated manuscript would be presented in the conference * TM of Rhone-Poulenc Ltd.
•8•
CisplaUn-gemcitabine, vs. cisplatin-gemcitabinevinorelbine, vs. cisplaUn-gemcitabine-paclitaxel in advanced non-small-cell lung cancer. First-stage analysis of a Southern Italy Cooperative Oncology Group (SlCOG) phase III trial
P. Comella, G. Frasci, N. Panza, G. Nicolella, L. Manzione, G. De Cataldis, R. Cioffi, E. Micillo, V. Lorusso, D. Bilancia, L. Maiorino, F.V. Piantedosi, A. Mangiameli, A. Gravina, A. Lamberti, M. De Lena, G. Cornelia. For the Southern Italy Cooperative Oncology Group
79
suits in advanced non-small cell lung cancer (NSCLC) patients. The present study aimed at comparing the PGV and PGT regimens with the cisplatin-gemcitabine (PG) combination. Patients and Methods: From October 1997, patients with locally advanced or metastatic disease NSCLC, aged <70 years and with ECOG PS _< 1, randomly received: cisplatin 50 mg/m2 + gemcitabine 1,000 mg/m 2 + vinorelbine 25 mg/m2 d 1 & 8 q 3 wk (PGV); cisplatin 100 mg/m 2 d 1 + gemcitabine 1,000 mg/m 2 d 1, 8, 15 q 4 wk (PG); cisplatin 50 mg/m2 + gemcitabine 1,000 mg/m2 + paclitaxe1125 mg/m 2 d 1 & 8 q 3 wk (PGT). Survival was the primary end-point of the study, and a final sample size of 120 patients per arm was set. An interim survival analysis was planned after the enroiment of 60 pts. Results: Until Sept. 30 1999, 247 patients (PG = 82, PGV = 84, PGT -- 81) had been enrolled (stage IIIB, 93; stage IV, 154). At that time the survival data of the first 60 pts. in each arm who had a >12week follow-up were analysed by an independent monitoring board. At an 11-month median follow-up 103 deaths have occurred, and the MST for the entire population is 48 weeks. The observed differences in survival between the 3 arms did not meet the criteria for the early stopping of the study. Conclusions: The accrual still continues. We expect to reach the final sample size within December '99, and to perform the final analysis in April 2000.
~ - - ~ Multi-center study with paclitaxel (P)lcarboplatin (C) in advanced or metastatic non-small cell lung cancer (NSGLC) patients (pts) P. Glorieux 1, P. Ortmanns 2, S. Marien 3, R. Degives4, D. Degraeve5, M. Potvin6, D. Grauwels 7, D. SchaUier7. 1Clin. Sud Luxembourg,
At/on; 2H. Fami/ie, Rumst; 3H. Hart, Lier; 4Bois de/'Abbaye, Seraing; 5St. Franciskus, Heusden-Zo/der; 6Van Enschodt, Boom; 7Bristo/_Myers Squibb, Belgium Purpose: To evaluate the efficacy and toxicity of paclitaxel (TAXOL®) at two different dose levels and carboplatin (PARAPLATIN®) for the treatment of chemonaive NSCLC patients stage IIIA-B and IV in a large multi-center setting. To evaluate the feasibility of carboplatin dosing via the Chatelut formula. Pts and Methods: Histologically documented NSCLC pts with measurable disease, an ECOG PS = 0-2. Treatment consisted of an every 3 weeks administration of P either at 175 mg/m_ or 200 mg/m_ by 3-hour IV infusion followed by C at an area under the concentration/time curve (AUC) = 6 using the Chatelut formula. Results: 144 pts were enrolled and data of 118 pts were available for this analysis:
N° pts median age (years) male/female Stage IIINIIIB/IV Histology SCC/ADC/LC/other Response (%) Time to progression (months) Median survival (months) One year survival Toxicity (NCIC CTC Gr 3-4) - Neutropenia - Thrombocytopenia - Neurotoxicity - Myalgia/arthrslgia - Febrile neutropenia
PC 200/6
PC 175/6
97 63.7 82/15 5139153
21 66.1 19/2 1/5/15
38/24/13•22 21/80 (27.5%) 4.3 8.8 36%
8/7/3/3 4/19 (21.0%) 3.7 6.7 32%
59% 14.5% 13% 7% 7%
48% 19% 5% 5% 5%
(S/COG); clo Tumor Institute of Naples, Italy Purpose: Both the cisplatin-gemcitabine-vinorelbine (PGV) and the cisplatin-gemcitabine-paclitaxel (PGT) regimens gave promising re-
Conclusion: This large multi-center study confirms the efficacy and safety of PC as first line treatment of stage IlIA-B/IV NSCLC at both