- Email: [email protected]
Sequential chemotherapy with carboplatin (C) and gemcitabine (G) followed by paclitaxel (P) in poor performance status (PS) and elderly patients (pts) with non-small cell lung cancer (NSCLC)
16
Chemotherapy/Paclitaxel
(n = 44) Non Small Cell Lung Cancer (NSCLC) patients in a phase II study to determine the efficacy and toxicity profile of the combination of Paclitaxel (225 mg/m2, 3-h infusion, day 1) followed by Carboplatin (AUC 6 mg/ml/min, day 1 according to the Calvertis formula). Other inclusion criteria were Performance Status ECOG 0-2, adequate organ function, measurable lesions and written informed consent. Patients with symptomatic brain metastasis and active infection were excluded. Patients on day 1 received standard antiemetic protection and antiallergic premedication, 1-hr before paclitaxel administration. The treatment was repeated every 3 weeks up to a total of 6 cycles. Results: Major clinical characteristics were: 75% male, median age 61 yrs. (range 34-74); 75% stage IV'; 46% adenocarcinomas, 30% squamous cell carcinomas, 8% large cell carcinomas and 16% with only cytological diagnosis of NSCLC. In 57 patients evaluable for response 1 patients achieved a CR (2%), 26 a PR (46%) for an overall RR of 47% (95 C.I. 33.7-59.3, Stage IIIB = 53%, Stage IV = 45%). 22 patients had SD (39%) and 8 had PD (14%). The median progression free survival was 22 weeks and median survival time, 52 weeks. The 1-year survival rate was 50%. 59 patients were evaluable for toxicity. Grade 3-4 granulocytopenia, anemia and thrombocytopenia were observed in 66%, 2% and 3% respectively. Non hematological toxicities included nausea, alopecia, myalgia/arthralgia, peripheral neuropathy and asthenia. Some of these toxicities showed a cumulative effect. Conclusion: The Carboplatin-Paclitaxel combination at the doses tested is active and well tolerated in advanced previously untreated NSCLC
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Phase II multicenter randomized trial of induction weekly paclitaxel (P) administered in combination with carboplatin (C) followed by weekly maintenance P vs. observation for patients (pts.) with advanced & metastatic non-small cell lung cancer (NSCLC)
C.P. Belani 1, J. Barstis 2, R. Clark 3, G. Mills 4, M. Perry5, S. Nattam 6.
1Univ of Pittsburgh, PA; 2UCLA, CA; 3Hem-Onc Associates, Rockville, MD; 4LSUMC, Shreveport, LA; 5EIlis Fischel Cancer Center, Columbia, MO; 6Fort Wayne Medical Oncology-Hematology, IN, USA This study was designed to explore the efficacy, safety, dose-density and dose-intensity of three different schedules of weekly P and C for pts. with previously untreated advanced and metastatic NSCLC. On arm I, P was administered at 100 mg/m2/week (wk.) for three weeks (wks.) with the fourth wk. off and C was given at AUC = 6 on day 1 (4 cycles); on arm II, both P (100 mg/m 2) and C (AUC = 2) were administered weekly for three wks. with the fourth wk. off (4 cycles); on arm III, P (150 mg/m 2) and C (AUC = 2) weekly for six wks. with two wks. off and then P 100 mg/m2/wk, for six wks. with weekly C (AUC = 2) for six wks. with two wks. off. Following 16 wks. of this induction therapy, pts. with a complete response (CR), partial response (PR) or stable disease (SD) were further randomized to maintenance P (70 mg/m2/wk.) vs observation.
# Patients Median Age (yrs) Male/Female (%) Stage - IIIB/IV (%) Performance Status 0/1/2 (%) Efficacy CR (%) PR (%) SD (%) Toxicity Neutropenia 9r. 4 (%) Thrombocytopenia gr. 4 (%) Neuropathy gr. 3 (%) Vomiting 9r. 3 (%) Febrile Neutropenia gr. 4 (%)
Arm I
Arm II
Arm III
71 66 63/37 24/76 24/62/14
70 60 66/34 21/79 30/58/12
67 64 62/38 22/78 24/63/13
3 (4) 20 (28) 16 (25)
2 (3) 23 (33) 11 (16)
1 (2) 16 (24) 18 (27)
6 1 2 2 0
5 (7) 2 (3) 2 (3) 2 (3) 1 (1)
4 (6) 0 6 (9) 4 (6) 0
(9) (1) (3) (3)
The study has enrolled 314 pts., and 76 pts. have been randomized to the maintenance phase as of 12/99. Preliminary demographic, efficacy and toxicity data at interim analysis on the first 208 pts. (induction phase) are given in the Table. The three weekly regimens of P in combination with C are feasible and well tolerated. The final analyses of efficacy, toxicity, dose-density and dose-intensity will be available for presentation in September 2000. (Supported by Bristol-Myers Squibb.)
r•]
Phase ii study of oxaliplatin (O) and paclitaxel (T) in advanced Non-Small Cell Lung Cancer (NSCLC)
A.M. Mauer, G.A. Otterson, L.L. Szeto, P,C. Hoffman, E.E. Vokes.
University of Chicago Phase II Network, Chicago, IL; Ohio State University, Columbus, OH; University of Chicago Medical Center, Chicago, IL, USA Platinum and taxane combinations are among the most active regimens reported for the treatment of advanced NSCLC. Oxaliplatin, a novel antineoplasUc platinum derivative with a DACH carrier ligand, demonstrates preclinical activity in many tumor cell lines including some that are resistant to cisplatin and carboplatin. Based upon in vitro studies demonstrating synergistic anti-tumor activity between oxaliplatin and paclitaxel, as well as the non-overlapping toxicities of these agents, study of their combination is warranted. We have undertaken a phase II study to evaluate the combination of oxaliplatin and paclitaxel in advanced NSCLC. The treatment schedule and doses for this phase II study are based upon a phase I investigation of the combination in patients with heavily pretreated advanced ovarian cancer (Pro Amer Soc Clin Oncol 17: 357a, 1998). Eligibility criteria include: stage IIIB (with pleural effusion) or stage IV NSCLC with measurable disease, no prior chemotherapy, and ECOG performance status 0-2, and adequate hematologic, renal and hepatic function. Protocol therapy includes: paclitaxel 175 mg/m2 administered as a 1-hour infusion and oxaliplatin 130 mg/rn2 administered as a 2-hour infusion every 3 weeks. To date, four patients have been enrolled in this study and no grade 3 or 4 toxicities have been encountered. Antitumor activity has been documented. Accrual to this phase II study continues to define this regimenis toxicity and activity in NSCLC with a targeted total accrual of 14-40 patients. Sponsored by NCI Grant #1U01CA63187-01
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Sequential chemotherapy with carboplatin (C) and gemcitabine (G) followed by paclitaxel (P) in poor performance status (PS) and elderly patients (pts) with non-small cell lung cancer (NSCLC)
M.J. Edelman, D.R. Gandara, D. Lau, P. Lara, I. Lauder. University of Maryland Greenebaum Cancer Center, Baltimore, MD; University of California, Davis; VA Northern California Health Care System, USA
Purpose: In a recent trial, we evaluated the concept of sequential chemotherapy in the treatment of advanced NSCLC by administration of three cycles of C/G followed by three cycles of P (PASCO 2000). ECOG (E-1594) indicated that patients (pts) with PS = 2 may have increased toxicity and poor response to chemotherapy (Johnson, PASCO 18:461a, 1999). Additionally, many question the value of chemotherapy in pts of age > 70. This paper evaluates the effects of chemotherapy in those special populations. Patients and Methods: Pts with Stage IIIb (pleural effusion)/Stage IV NSCLC and SWOG performance status of 2 or age > 70 years were evaluated. Therapy consisted of three cycles of C AUC = 6 mg/ml x rain day 1 and G 1000 mg/m2 dl, 8 every 21 days followed by three cycles of P 225 mg/m2 (3 hrs) every 21 days. Results: A total of 21 patients were enrolled: 10 pts with PS = 2; 9 pts age > 70; 2 pts with both PS = 2 and >70. Worst toxicity/pt for pts with PS = 2 was grade 3/4 neutropenia: 5, grade 3/4 platelets: 3, grade 3 infection: 1 for the C/G portion, and grade 3/4 neutropenia: 2, and infection: 1 for the paclitaxel portion. There was one cardiac death on paclitaxel, possibly related to therapy. 8/10 pts completed the first
Chemotherapy/Paclitaxel three cycles and 6/10 completed all 6 cycles of therapy. 9 pts in this group were evaluable for response and there were 2PR/1CR. Survival for pts with PS = 2 was 6.4 months. Pts age > 70 also had acceptable toxicity with grade 3/4 neutropenia: 2, Pits: 2, infection: 1 for the C/G portion, and grade 3/4 neutropenia: 2 on the paclitaxel portion. 7/9 pts completed the first three cycles and 5/9 completed all six cycles. There was 1CR/1PR. Median survival was 13.6 months. Conclusions: The sequential regimen of carboplatin/gemcitabine followed by paclitaxel has acceptable toxicity and promising response and survival in patients with PS = 2 or age > 70 years, The result for PS = 2 pts is comparable, if not superior to, the recent results of several regimens reported by ECOG in terms of response and survival. Though the overall rate of grade 3/4 toxicity was similar to the ECOG, these were mostly laboratory abnormalities and the majority of pts recovered sufficiently to receive further treatment. However, the numbers are small. Further evaluation of this regimen in these populations is warranted. Supported by Eli Lilly Oncology
~-0~ls cisplatin necessary for the treatment of non-small cell lung cancer (NSCLC)? - Analysis of consecutive trials of paclitaxel in NSCLC K. Kubota 1, ¥. Nishiwaki 1, A. Yokoyama2, S. Yoneda3, T. Tamura4, K. Watanabe 5, N. Saijo4. 1National Cancer Center Hospital East; 2Niigata Cancer Center Hospital; 3Saitama Cancer Center; 4National Cancer Center Hospital; 5 Yokohama Municipal Citizen's Hospital, Japan Paclitaxel (P) has unique mechanisms of action and is active in NSCLC. Because benefit of combination chemotherapy of P with other agents has not been demonstrated, we conducted an analysis of consecutive trials of P, which included phase II study of P alone and P/cisplatin. In P alone study, 210 mg/m 2 of P was administered as 3-hour infusion and repeated at 21-day interval. Eighty mg/m 2 of cisplatin and 180 mg/m 2 of P (3-hour infusion) were repeated at 21day interval in P/cisplatin study. Eligibility criteria are similar between two studies except for PS (0-2 in P alone, 0-1 in P/cisplatin) and stage (inoperable IIIA/IIIB and IV in P alone, IIIB and IV in P/cisplatin). Baseline demographics of the total 92 patients (pts), response and toxicities are summarized.
No. of pts Median age (range) Male (%) PS 0/1/2 Adeno/Squamous/others IIINIIIB/IV Response rate (%) Neutropenia Grade 3 + 4 (%) Nausea and vomiting (%) Peripheral neuropathy (%)
Paclitaxel alone
Paclitaxel/cisplatin
60 63 (27-74) 45 (75) 14/38/8 41/14/5 5/6/49 38 82 28 70
32 61 (43-:,71) 22 (69) 9/23/27/4/1 -/5/27 31 53 78 47
Survival data will be presented at the meeting. There was no difference in response rate between the two studies. Adding of cisplatin failed to show an advantage over P alone. In conclusion, randomized trials of paclitaxel with or without cisplatin are warranted.
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17
Paclitaxel and cisplatin in stage IV non-small cell lung cancer: A GETICS phase II study
A.V. Jaremtchuk, E,E Aman, J.J. Zarba, M Salvadori, R. Alvarez, F. Marmissolle. GETICS, Comodoro Rivadavia; GETICS, Buenos Aires; GETICS, Yerba Buena; GETICS, Santa Rosa; GETICS (Grupo de Estudio Tratamiento e InvestigaciOn del C.ncar del Sur), Argentina
Background: Stage is one of the most important prognostic factors in NSCLC. Unfortunately several studies evaluate chemotherapy regimens in advanced disease pooled stage III and IV patients. Purpose: To evaluate the efficacy, toxicity and survival rate of stage IV NSCLC patients treated with paclitaxel-cisplatin combination. Patients and Methods: Chemotherapy-naive patients with histologically confirmed satge IV NSCLC, ECOG PS 0-1, adequate bone marrow and organ function and measurable disease were eligible for the study. Paclitaxel was administered at a dose of 175 rag/m2, threehour e.v. infusion on day 1 followed by Cisplatin at a dose of 100 rag/m2 with appropriate hydration on day 2. Treatment was repeated every 3 weeks. Results: Thirty-two patients were enrolled, median age was 54 years (range 36 to 74 years). Seventy-five percent of patients were males, 50% had edenocarcinoma and 31% had >10% weight loss. Ninety-one courses were administered and 28 patients received at least two courses of PC regimen. One patient achieved a complete response and 7 patients achieved a partial response for an overall response rate of 25%. The median time to progression, median survival time and one year survival rate were 25 weeks, 41 weeks and 28% respectively. Grade 3/4 leucopenia, thrombocytopenia and anemia were observed in 21%, 6% and 6%. Neuretoxicity grade 2 were observed in 12.5% of patients. No toxic deaths were reported. Conclusion: The data show that paclitaxel plus cisplatin is a welltolerated and active regimen in stage IV NSCLC patients,
15-• Phase II study of paclitaxel, ifosfamide and carboplaUn with fllgrastim support in advanced non-small cell lung cancer (NSCLC)
A.M. Mauer, R.H. Ansari, P.C. Hoffman, T.G. Gabrys. University of Chicago Phase II Network, Chicago, IL, USA Based on the activity observed with the doublet combinations of paclitaxel/carboplatin and paclitaxel/ifosfamide (Annals Oncol 1996, 7: 314-6) in NSCLC, we undertook a phase II study of the triplet combination of paclitaxel, ifosfamide, and carboplatin in patients with advanced NSCLC. Doses and schedule of therapy were based upon phase I study of the triplet regimen completed at our institution. The regimen included paclitaxel (200 mg/m2 per 1 hour on day 1), carboplatin (AUC = 5 on day 2), and ifosfamicle (1500 mg/m2 on days 1 & 2) with Mesna (300 mg/m2 on days 1 & 2) with prophylactic filgrastim support starting on day 4 until ANC > 10,000. Eligibility criteria included stage IIIB (pleural efffusion)/IV NSCLC, measurable disease, normal bone marrow, hepatic, renal function. Patients were allowed to have to have one prior therapy with an investigational agent. Asymptomatic brain metastases were allowed. Fifty patients received protocol therapy. Pt characteristics: male-32; female-18; median age 62; median CALGB performance status-I; stage IIIB-8/IV-42; prior single agent experimental chemotherapy-I; prior chest radiotherapy-2. Median number of cycles administered was 4. Grade 4 hematologic toxicity included thrombocytopenia (6 pts) and neutropenia (7 pts) with neutropenic fever in 1 patient. Non-hematologic toxicity grade > 3 included: vomiting (3 pts), reversible azotemia (grade 3-1 pt), peripheral neuropathy (5 pts) and neurocortical (2 pts). Out of the 42 patients assessed for response, 10 partial responses were noted for an overall response rate of 24%. At a median follow up time of 11.3 months, the median survival is 13.4 months. This large phase II study confirms the feasibility and activity of this triplet regimen in patients with advanced non-small cell lung cancer.
Chemotherapy/Paclitaxel
(n = 44) Non Small Cell Lung Cancer (NSCLC) patients in a phase II study to determine the efficacy and toxicity profile of the combination of Paclitaxel (225 mg/m2, 3-h infusion, day 1) followed by Carboplatin (AUC 6 mg/ml/min, day 1 according to the Calvertis formula). Other inclusion criteria were Performance Status ECOG 0-2, adequate organ function, measurable lesions and written informed consent. Patients with symptomatic brain metastasis and active infection were excluded. Patients on day 1 received standard antiemetic protection and antiallergic premedication, 1-hr before paclitaxel administration. The treatment was repeated every 3 weeks up to a total of 6 cycles. Results: Major clinical characteristics were: 75% male, median age 61 yrs. (range 34-74); 75% stage IV'; 46% adenocarcinomas, 30% squamous cell carcinomas, 8% large cell carcinomas and 16% with only cytological diagnosis of NSCLC. In 57 patients evaluable for response 1 patients achieved a CR (2%), 26 a PR (46%) for an overall RR of 47% (95 C.I. 33.7-59.3, Stage IIIB = 53%, Stage IV = 45%). 22 patients had SD (39%) and 8 had PD (14%). The median progression free survival was 22 weeks and median survival time, 52 weeks. The 1-year survival rate was 50%. 59 patients were evaluable for toxicity. Grade 3-4 granulocytopenia, anemia and thrombocytopenia were observed in 66%, 2% and 3% respectively. Non hematological toxicities included nausea, alopecia, myalgia/arthralgia, peripheral neuropathy and asthenia. Some of these toxicities showed a cumulative effect. Conclusion: The Carboplatin-Paclitaxel combination at the doses tested is active and well tolerated in advanced previously untreated NSCLC
I~
Phase II multicenter randomized trial of induction weekly paclitaxel (P) administered in combination with carboplatin (C) followed by weekly maintenance P vs. observation for patients (pts.) with advanced & metastatic non-small cell lung cancer (NSCLC)
C.P. Belani 1, J. Barstis 2, R. Clark 3, G. Mills 4, M. Perry5, S. Nattam 6.
1Univ of Pittsburgh, PA; 2UCLA, CA; 3Hem-Onc Associates, Rockville, MD; 4LSUMC, Shreveport, LA; 5EIlis Fischel Cancer Center, Columbia, MO; 6Fort Wayne Medical Oncology-Hematology, IN, USA This study was designed to explore the efficacy, safety, dose-density and dose-intensity of three different schedules of weekly P and C for pts. with previously untreated advanced and metastatic NSCLC. On arm I, P was administered at 100 mg/m2/week (wk.) for three weeks (wks.) with the fourth wk. off and C was given at AUC = 6 on day 1 (4 cycles); on arm II, both P (100 mg/m 2) and C (AUC = 2) were administered weekly for three wks. with the fourth wk. off (4 cycles); on arm III, P (150 mg/m 2) and C (AUC = 2) weekly for six wks. with two wks. off and then P 100 mg/m2/wk, for six wks. with weekly C (AUC = 2) for six wks. with two wks. off. Following 16 wks. of this induction therapy, pts. with a complete response (CR), partial response (PR) or stable disease (SD) were further randomized to maintenance P (70 mg/m2/wk.) vs observation.
# Patients Median Age (yrs) Male/Female (%) Stage - IIIB/IV (%) Performance Status 0/1/2 (%) Efficacy CR (%) PR (%) SD (%) Toxicity Neutropenia 9r. 4 (%) Thrombocytopenia gr. 4 (%) Neuropathy gr. 3 (%) Vomiting 9r. 3 (%) Febrile Neutropenia gr. 4 (%)
Arm I
Arm II
Arm III
71 66 63/37 24/76 24/62/14
70 60 66/34 21/79 30/58/12
67 64 62/38 22/78 24/63/13
3 (4) 20 (28) 16 (25)
2 (3) 23 (33) 11 (16)
1 (2) 16 (24) 18 (27)
6 1 2 2 0
5 (7) 2 (3) 2 (3) 2 (3) 1 (1)
4 (6) 0 6 (9) 4 (6) 0
(9) (1) (3) (3)
The study has enrolled 314 pts., and 76 pts. have been randomized to the maintenance phase as of 12/99. Preliminary demographic, efficacy and toxicity data at interim analysis on the first 208 pts. (induction phase) are given in the Table. The three weekly regimens of P in combination with C are feasible and well tolerated. The final analyses of efficacy, toxicity, dose-density and dose-intensity will be available for presentation in September 2000. (Supported by Bristol-Myers Squibb.)
r•]
Phase ii study of oxaliplatin (O) and paclitaxel (T) in advanced Non-Small Cell Lung Cancer (NSCLC)
A.M. Mauer, G.A. Otterson, L.L. Szeto, P,C. Hoffman, E.E. Vokes.
University of Chicago Phase II Network, Chicago, IL; Ohio State University, Columbus, OH; University of Chicago Medical Center, Chicago, IL, USA Platinum and taxane combinations are among the most active regimens reported for the treatment of advanced NSCLC. Oxaliplatin, a novel antineoplasUc platinum derivative with a DACH carrier ligand, demonstrates preclinical activity in many tumor cell lines including some that are resistant to cisplatin and carboplatin. Based upon in vitro studies demonstrating synergistic anti-tumor activity between oxaliplatin and paclitaxel, as well as the non-overlapping toxicities of these agents, study of their combination is warranted. We have undertaken a phase II study to evaluate the combination of oxaliplatin and paclitaxel in advanced NSCLC. The treatment schedule and doses for this phase II study are based upon a phase I investigation of the combination in patients with heavily pretreated advanced ovarian cancer (Pro Amer Soc Clin Oncol 17: 357a, 1998). Eligibility criteria include: stage IIIB (with pleural effusion) or stage IV NSCLC with measurable disease, no prior chemotherapy, and ECOG performance status 0-2, and adequate hematologic, renal and hepatic function. Protocol therapy includes: paclitaxel 175 mg/m2 administered as a 1-hour infusion and oxaliplatin 130 mg/rn2 administered as a 2-hour infusion every 3 weeks. To date, four patients have been enrolled in this study and no grade 3 or 4 toxicities have been encountered. Antitumor activity has been documented. Accrual to this phase II study continues to define this regimenis toxicity and activity in NSCLC with a targeted total accrual of 14-40 patients. Sponsored by NCI Grant #1U01CA63187-01
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Sequential chemotherapy with carboplatin (C) and gemcitabine (G) followed by paclitaxel (P) in poor performance status (PS) and elderly patients (pts) with non-small cell lung cancer (NSCLC)
M.J. Edelman, D.R. Gandara, D. Lau, P. Lara, I. Lauder. University of Maryland Greenebaum Cancer Center, Baltimore, MD; University of California, Davis; VA Northern California Health Care System, USA
Purpose: In a recent trial, we evaluated the concept of sequential chemotherapy in the treatment of advanced NSCLC by administration of three cycles of C/G followed by three cycles of P (PASCO 2000). ECOG (E-1594) indicated that patients (pts) with PS = 2 may have increased toxicity and poor response to chemotherapy (Johnson, PASCO 18:461a, 1999). Additionally, many question the value of chemotherapy in pts of age > 70. This paper evaluates the effects of chemotherapy in those special populations. Patients and Methods: Pts with Stage IIIb (pleural effusion)/Stage IV NSCLC and SWOG performance status of 2 or age > 70 years were evaluated. Therapy consisted of three cycles of C AUC = 6 mg/ml x rain day 1 and G 1000 mg/m2 dl, 8 every 21 days followed by three cycles of P 225 mg/m2 (3 hrs) every 21 days. Results: A total of 21 patients were enrolled: 10 pts with PS = 2; 9 pts age > 70; 2 pts with both PS = 2 and >70. Worst toxicity/pt for pts with PS = 2 was grade 3/4 neutropenia: 5, grade 3/4 platelets: 3, grade 3 infection: 1 for the C/G portion, and grade 3/4 neutropenia: 2, and infection: 1 for the paclitaxel portion. There was one cardiac death on paclitaxel, possibly related to therapy. 8/10 pts completed the first
Chemotherapy/Paclitaxel three cycles and 6/10 completed all 6 cycles of therapy. 9 pts in this group were evaluable for response and there were 2PR/1CR. Survival for pts with PS = 2 was 6.4 months. Pts age > 70 also had acceptable toxicity with grade 3/4 neutropenia: 2, Pits: 2, infection: 1 for the C/G portion, and grade 3/4 neutropenia: 2 on the paclitaxel portion. 7/9 pts completed the first three cycles and 5/9 completed all six cycles. There was 1CR/1PR. Median survival was 13.6 months. Conclusions: The sequential regimen of carboplatin/gemcitabine followed by paclitaxel has acceptable toxicity and promising response and survival in patients with PS = 2 or age > 70 years, The result for PS = 2 pts is comparable, if not superior to, the recent results of several regimens reported by ECOG in terms of response and survival. Though the overall rate of grade 3/4 toxicity was similar to the ECOG, these were mostly laboratory abnormalities and the majority of pts recovered sufficiently to receive further treatment. However, the numbers are small. Further evaluation of this regimen in these populations is warranted. Supported by Eli Lilly Oncology
~-0~ls cisplatin necessary for the treatment of non-small cell lung cancer (NSCLC)? - Analysis of consecutive trials of paclitaxel in NSCLC K. Kubota 1, ¥. Nishiwaki 1, A. Yokoyama2, S. Yoneda3, T. Tamura4, K. Watanabe 5, N. Saijo4. 1National Cancer Center Hospital East; 2Niigata Cancer Center Hospital; 3Saitama Cancer Center; 4National Cancer Center Hospital; 5 Yokohama Municipal Citizen's Hospital, Japan Paclitaxel (P) has unique mechanisms of action and is active in NSCLC. Because benefit of combination chemotherapy of P with other agents has not been demonstrated, we conducted an analysis of consecutive trials of P, which included phase II study of P alone and P/cisplatin. In P alone study, 210 mg/m 2 of P was administered as 3-hour infusion and repeated at 21-day interval. Eighty mg/m 2 of cisplatin and 180 mg/m 2 of P (3-hour infusion) were repeated at 21day interval in P/cisplatin study. Eligibility criteria are similar between two studies except for PS (0-2 in P alone, 0-1 in P/cisplatin) and stage (inoperable IIIA/IIIB and IV in P alone, IIIB and IV in P/cisplatin). Baseline demographics of the total 92 patients (pts), response and toxicities are summarized.
No. of pts Median age (range) Male (%) PS 0/1/2 Adeno/Squamous/others IIINIIIB/IV Response rate (%) Neutropenia Grade 3 + 4 (%) Nausea and vomiting (%) Peripheral neuropathy (%)
Paclitaxel alone
Paclitaxel/cisplatin
60 63 (27-74) 45 (75) 14/38/8 41/14/5 5/6/49 38 82 28 70
32 61 (43-:,71) 22 (69) 9/23/27/4/1 -/5/27 31 53 78 47
Survival data will be presented at the meeting. There was no difference in response rate between the two studies. Adding of cisplatin failed to show an advantage over P alone. In conclusion, randomized trials of paclitaxel with or without cisplatin are warranted.
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17
Paclitaxel and cisplatin in stage IV non-small cell lung cancer: A GETICS phase II study
A.V. Jaremtchuk, E,E Aman, J.J. Zarba, M Salvadori, R. Alvarez, F. Marmissolle. GETICS, Comodoro Rivadavia; GETICS, Buenos Aires; GETICS, Yerba Buena; GETICS, Santa Rosa; GETICS (Grupo de Estudio Tratamiento e InvestigaciOn del C.ncar del Sur), Argentina
Background: Stage is one of the most important prognostic factors in NSCLC. Unfortunately several studies evaluate chemotherapy regimens in advanced disease pooled stage III and IV patients. Purpose: To evaluate the efficacy, toxicity and survival rate of stage IV NSCLC patients treated with paclitaxel-cisplatin combination. Patients and Methods: Chemotherapy-naive patients with histologically confirmed satge IV NSCLC, ECOG PS 0-1, adequate bone marrow and organ function and measurable disease were eligible for the study. Paclitaxel was administered at a dose of 175 rag/m2, threehour e.v. infusion on day 1 followed by Cisplatin at a dose of 100 rag/m2 with appropriate hydration on day 2. Treatment was repeated every 3 weeks. Results: Thirty-two patients were enrolled, median age was 54 years (range 36 to 74 years). Seventy-five percent of patients were males, 50% had edenocarcinoma and 31% had >10% weight loss. Ninety-one courses were administered and 28 patients received at least two courses of PC regimen. One patient achieved a complete response and 7 patients achieved a partial response for an overall response rate of 25%. The median time to progression, median survival time and one year survival rate were 25 weeks, 41 weeks and 28% respectively. Grade 3/4 leucopenia, thrombocytopenia and anemia were observed in 21%, 6% and 6%. Neuretoxicity grade 2 were observed in 12.5% of patients. No toxic deaths were reported. Conclusion: The data show that paclitaxel plus cisplatin is a welltolerated and active regimen in stage IV NSCLC patients,
15-• Phase II study of paclitaxel, ifosfamide and carboplaUn with fllgrastim support in advanced non-small cell lung cancer (NSCLC)
A.M. Mauer, R.H. Ansari, P.C. Hoffman, T.G. Gabrys. University of Chicago Phase II Network, Chicago, IL, USA Based on the activity observed with the doublet combinations of paclitaxel/carboplatin and paclitaxel/ifosfamide (Annals Oncol 1996, 7: 314-6) in NSCLC, we undertook a phase II study of the triplet combination of paclitaxel, ifosfamide, and carboplatin in patients with advanced NSCLC. Doses and schedule of therapy were based upon phase I study of the triplet regimen completed at our institution. The regimen included paclitaxel (200 mg/m2 per 1 hour on day 1), carboplatin (AUC = 5 on day 2), and ifosfamicle (1500 mg/m2 on days 1 & 2) with Mesna (300 mg/m2 on days 1 & 2) with prophylactic filgrastim support starting on day 4 until ANC > 10,000. Eligibility criteria included stage IIIB (pleural efffusion)/IV NSCLC, measurable disease, normal bone marrow, hepatic, renal function. Patients were allowed to have to have one prior therapy with an investigational agent. Asymptomatic brain metastases were allowed. Fifty patients received protocol therapy. Pt characteristics: male-32; female-18; median age 62; median CALGB performance status-I; stage IIIB-8/IV-42; prior single agent experimental chemotherapy-I; prior chest radiotherapy-2. Median number of cycles administered was 4. Grade 4 hematologic toxicity included thrombocytopenia (6 pts) and neutropenia (7 pts) with neutropenic fever in 1 patient. Non-hematologic toxicity grade > 3 included: vomiting (3 pts), reversible azotemia (grade 3-1 pt), peripheral neuropathy (5 pts) and neurocortical (2 pts). Out of the 42 patients assessed for response, 10 partial responses were noted for an overall response rate of 24%. At a median follow up time of 11.3 months, the median survival is 13.4 months. This large phase II study confirms the feasibility and activity of this triplet regimen in patients with advanced non-small cell lung cancer.