A phase I study of navelbine (NVB) - carboplatin (CBDCA) combination in non small cell lung cancer...
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437 CISPLATIN, IFOSFALMIDE WITH INCREASING DOSAGES OF VJNORELBINE (NIP) IN ADVANCED NON SMALL CELL LUNG CANCER (NSCLC). P.J.SOUQUET*, P.FOURNEL** C.H.BOHAS**, ICOURT FORTUNE**, A.EMONOT**, JP.BERNARD*. *Unity of Thoracic Oncology CH LYON SUD, 69310 PIERRE-BEMTE FRANCE - ** Unity of Thoracic Oncology St Etien?re Nord 42277 FRANCE We conducted a phase II trial (in two institutions) of the association CISPLATIN 75mg/m* Dl,IFOSFAMIDE 3g/m2 Dl all 21 days with various domges of VINORELBINE (v) (A : V 25mg/m2D1B:V25mg/m DlandS;C:V25mg/m Dland 15, V 12,5 mg/m* DS), in histologically proved NSCLC of stage III B and IV. Assessment of tbe response was performed 3 weeks after the third course (by fiberoptic bronchoscopy, and chest CT). Thoracic Radiotherapy was performed in stage III B after these 3 courses (2 Gy/fiaction, 5 Bactions/week 5 weeks) and in stage IV 3 more courses were performed in case of objective response. Croup A : 34 patients : after 3 courses 2 CR, 10 PR objective response 35%. Any haematological toxicity, 1 Neurotoxicity (confusion/related to Ifosfamide, 1 transient renal insufficiency related to Cisplatin Groupe B 26 patients 4 objective response in the 10 first evaluable patients. In Groupe C : inclusion is still on going Definitive results will be presented and especially tbe comparative results and toxicity between tbe 3 groups and tbe dose intensity of VINORELBINE in the three groups. 439 IFy)SFAhlIDE (IFX) and NAVELBINE (NVB) FOR UNRESECTABLE NON SMALL CELL LUNG CANCER RJSCLC). J.M. Morere, L. Israel, A. Brunet, C. Eoaxix, J.L. Breau. Clinique d’fhrcologie Medicale, H6pital Avicenne, Bobigny, France. 29 patients with unresectable NSCLC received a first line regimen of IFX 2 g/m*/day, plus mesna I,5 g/ma/day, day 1 to day 3, and NVE 25 mg/m*/day, day 1 and day 8. One course was done every 3 weeks. Leucocyte and platelets count were obtained weekly. IFN and NVB were reduced by 20 96 in case of myelosuppmasion. Reponse was assessed after 2 courses. Patients characteristics included : age 65 years (38-73) ; ECQG performance status (PS) PSI : 16 ; PS2 : 11 ; PSO:3;stageIIIa:l;stageIIIb:17;stageIV:12.1patientwas not evaluated for response due to poor compliance. 10 partial responses were achieved (34 96). Median number of treatment cycles was 4 (1-16). ECOG grade 3 or 4 leucopenia occurred in 6/29 patients (20 96). 1 patient died in neutmpenia. Non hematologic toxicity consisted of alopecia : 20 96 ; bronchospasm : 1, myalgia : 1 ; encephalopatby : 1 ; cutaneous reaction : 1. IFX plus NVR is effective in NSCLC. Due to its lack of renal toxicity it is feasible when a platinum-based therapy is not possible. 115 438 A PHASE I STUDY OF NAVELBINE (NM) - CARBOPLATIN ICBDCAl COMBINATION IN NON SMALL CELL LUNG CANCER (NSCLC). P. Jacoulet. JL. Breton. 0. Gamier. V. West~l. A. Dwierre. Beran~on-&ort, FRANCE. In NSCLC, NVB is a new promising agent with a high objective response rate (OR) in phase II studies (29 %, 95 Cl : 20-38 %I. Its dose limiting toxicity is nrutropania. In a phase Ill study (ECCO 7, 1993, A881). NV8 + Cisplatin, compared to NVB alone, shown a significantly higher OR rate with no gain on survival. This could be explained by a greater toxicity of the combination. Particularly, 32 % of patients who achieved OR, discontinued their treatment during the response. In order to decrease the combination toxicitY, we initiated a phase I study of NVB-CBDCA to find the optimal dose of CBDCA with a standard dose of NVB (30 mg/m’ , D,-D,, q3wl. Eligibility criteria were as follows : histologically proved NSCLC, no previous treatment, stage lllb and IV, with at least one measurable lesion. Asympto- matic brain metastasis could be included ; patients had to be 5 75 years old with a PS <_ 3. Patients ware treated at four dose levels of CBDCA : 275, 300, 325, 350 mglmz, D,, q3w. “ODtS 275 7 300 7 325 3 350 4 Leucopenia Dose-intensity Thrombopenia OR Toxic G41n”cycles of NVB G3/4 deaths 5/36 I1 4 %I 84.9 % 2/36 2 0 2/28 1 7 %I 95.8 % l/28 1 2 10126 (38 %) 76.5 % 2126 2 1 205 - 60.3 % 1115 0 0 OR were observed at each level. The dose intensity of NVB fell from 325 mglm2, owing to attenuations of doses due to myalosuppression. We recommand this schedula : NVB : 30 mg/mz, D,-D,, CBDCA 300 mglm’ , D,, each cycle repeated every 3 weeks. in order to keep up the dose-intensity of NVB. 440 SPANISH LUNG CANCER GROUP VINORELBINE PHASE II TRIAL JN NON-SAMLL CELL LUNG CANCER (NSCLC): LACK OF DEMONSTRABLE ACTIVITY WITH A BIWEEKLY SCHEDULE. C. A. Font, A. Ant&t, A. GW&nez, E. ArMda. B. Massad, A. Des, C. &dell, A. War, E. Blanco, M.GLParedes,** J.J. Sdnchez,+*M. R&i.** .*H. Genemll de Valencia andSpMish Lug CIzncer Gmup. Spain. *+Phannacia Vinorelbine (VRL), a new semisyntbetic vinea alkaloid, has been claimed to be a very active drug in NSCLC with 30% reapcmsemte in a phase 11trial (ASCO 88 vol 7, 778) but lower frequencies in phase III trials ran ’ g from 12% to 17% (ASCO 93, 1138, 1148). Between April 9?r and August 93, 72 NSCLC treatment-naive patients @a) were entered in the present trial to receive VRL iv 30 mg/m2 on days 1 and 8 every 3 weeks (w) for 6 or mom c cles (cy) in responding pts. The median number of courses was 3 ( -7). Four r pts were. excluded due to protocol violations. Demographic chara&ristics were: Median age 61 years(35-76), 66 male and 2 female, BCQG performance status rated: 0 in 20 pts, 1 in 40 and 2 in 8. Squamous cell carcinoma was diagnosed in 58%pts, adenoeareinoma in 22.5% and large cell in 19.5%.40 pts were stage IV, 19 IIIB, 5 IIIA and 4 II. Response was evaluated according to WHO criteria in 48 pts who had me&&3 cy. Partial response was seen in 3 pts (6%) (%%CI=1.3-17.2). Stable disease was observed in 21 pts (43.7%) and progressive disease in 24 pts (50%). Median survival was 26.7~ and median time to progression 13.8~. 68 pts were evaluable for toxicity with 222 cy administered. Hematologieal tests wem. performed on days. 1, 8, 14, and 21. Gmde 3-4 neu~,leucopenra and anemra were meorded m 4.9%, 2:9% and 1 of the hematologrcal counts resPe&wely. Four pts requned hospitalization for drug-related infections. Grade 34 nausea and vomiting was seen in only 1 pt, and grade 3-4 alopecia in 3 pts. Severe neurotoxicity was not observed. Dose intensity was 20 mg/m2/w. In conclusion, the role of VRL in NSCL when used as single agent in a biweekly schedule should be regarded with caution.
Transcript of A phase I study of navelbine (NVB) - carboplatin (CBDCA) combination in non small cell lung cancer...
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CISPLATIN, IFOSFALMIDE WITH INCREASING DOSAGES OF VJNORELBINE (NIP) IN ADVANCED NON SMALL CELL LUNG CANCER (NSCLC). P.J.SOUQUET*, P.FOURNEL** C.H.BOHAS**, ICOURT FORTUNE**, A.EMONOT**, JP.BERNARD*. *Unity of Thoracic Oncology CH LYON SUD, 693 10 PIERRE-BEMTE FRANCE - ** Unity of Thoracic Oncology St Etien?re Nord 42277 FRANCE
We conducted a phase II trial (in two institutions) of the association CISPLATIN 75mg/m* Dl,IFOSFAMIDE 3g/m2 Dl all 21 days with various domges of VINORELBINE (v) (A : V 25mg/m2D1B:V25mg/m DlandS;C:V25mg/m Dland 15, V 12,5 mg/m* DS), in histologically proved NSCLC of stage III B and IV. Assessment of tbe response was performed 3 weeks after the third course (by fiberoptic bronchoscopy, and chest CT). Thoracic Radiotherapy was performed in stage III B after these 3 courses (2 Gy/fiaction, 5 Bactions/week 5 weeks) and in stage IV 3 more courses were performed in case of objective response. Croup A : 34 patients : after 3 courses 2 CR, 10 PR objective response 35%. Any haematological toxicity, 1 Neurotoxicity (confusion/related to Ifosfamide, 1 transient renal insufficiency related to Cisplatin Groupe B 26 patients 4 objective response in the 10 first evaluable patients. In Groupe C : inclusion is still on going Definitive results will be presented and especially tbe comparative results and toxicity between tbe 3 groups and tbe dose intensity of VINORELBINE in the three groups.
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IFy)SFAhlIDE (IFX) and NAVELBINE (NVB) FOR UNRESECTABLE NON SMALL CELL LUNG CANCER RJSCLC). J.M. Morere, L. Israel, A. Brunet, C. Eoaxix, J.L. Breau. Clinique d’fhrcologie Medicale, H6pital Avicenne, Bobigny, France. 29 patients with unresectable NSCLC received a first line regimen of IFX 2 g/m*/day, plus mesna I,5 g/ma/day, day 1 to day 3, and NVE 25 mg/m*/day, day 1 and day 8. One course was done every 3 weeks. Leucocyte and platelets count were obtained weekly. IFN and NVB were reduced by 20 96 in case of myelosuppmasion. Reponse was assessed after 2 courses. Patients characteristics included : age 65 years (38-73) ; ECQG performance status (PS) PSI : 16 ; PS2 : 11 ; PSO:3;stageIIIa:l;stageIIIb:17;stageIV:12.1patientwas not evaluated for response due to poor compliance. 10 partial responses were achieved (34 96). Median number of treatment cycles was 4 (1-16). ECOG grade 3 or 4 leucopenia occurred in 6/29 patients (20 96). 1 patient died in neutmpenia. Non hematologic toxicity consisted of alopecia : 20 96 ; bronchospasm : 1, myalgia : 1 ; encephalopatby : 1 ; cutaneous reaction : 1. IFX plus NVR is effective in NSCLC. Due to its lack of renal toxicity it is feasible when a platinum-based therapy is not possible.
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A PHASE I STUDY OF NAVELBINE (NM) - CARBOPLATIN ICBDCAl COMBINATION IN NON SMALL CELL LUNG CANCER (NSCLC). P. Jacoulet. JL. Breton. 0. Gamier. V. West~l. A. Dwierre. Beran~on-&ort, FRANCE.
In NSCLC, NVB is a new promising agent with a high objective response rate (OR) in phase II studies (29 %, 95 Cl : 20-38 %I. Its dose limiting toxicity is nrutropania. In a phase Ill study (ECCO 7, 1993, A881). NV8 + Cisplatin, compared to NVB alone, shown a significantly higher OR rate with no gain on survival. This could be explained by a greater toxicity of the combination. Particularly, 32 % of patients who achieved OR, discontinued their treatment during the response. In order to decrease the combination toxicitY, we initiated a phase I study of NVB-CBDCA to find the optimal dose of CBDCA with a standard dose of NVB (30 mg/m’, D,-D,, q3wl. Eligibility criteria were as follows : histologically proved NSCLC, no previous treatment, stage lllb and IV, with at least one measurable lesion. Asympto- matic brain metastasis could be included ; patients had to be 5 75 years old with a PS <_ 3. Patients ware treated at four dose levels of CBDCA : 275, 300, 325, 350 mglmz, D,, q3w.
“ODtS
275 7 300 7 325 3 350 4
Leucopenia Dose-intensity Thrombopenia OR Toxic G41n”cycles of NVB G3/4 deaths
5/36 I1 4 %I 84.9 % 2/36 2 0 2/28 1 7 %I 95.8 % l/28 1 2
10126 (38 %) 76.5 % 2126 2 1 205 - 60.3 % 1115 0 0
OR were observed at each level. The dose intensity of NVB fell from 325 mglm2, owing to attenuations of doses due to myalosuppression. We recommand this schedula : NVB : 30 mg/mz, D,-D,, CBDCA 300 mglm’, D,, each cycle repeated every 3 weeks. in order to keep up the dose-intensity of NVB.
440
SPANISH LUNG CANCER GROUP VINORELBINE PHASE II TRIAL JN NON-SAMLL CELL LUNG CANCER (NSCLC): LACK OF DEMONSTRABLE ACTIVITY WITH A BIWEEKLY SCHEDULE. C. A. Font, A. Ant&t, A. GW&nez, E. ArMda. B. Massad, A. Des, C. &dell, A. War, E. Blanco, M.GLParedes,** J.J. Sdnchez,+*M. R&i.** .*H. Genemll de Valencia and SpMish Lug CIzncer Gmup. Spain. *+Phannacia
Vinorelbine (VRL), a new semisyntbetic vinea alkaloid, has been claimed to be a very active drug in NSCLC with 30% reapcmse mte in a phase 11 trial (ASCO 88 vol 7, 778) but lower frequencies in phase III trials ran ’ g from 12% to 17% (ASCO 93, 1138, 1148). Between April 9 ?r and August 93, 72 NSCLC treatment-naive patients @a) were entered in the present trial to receive VRL iv 30 mg/m2 on days 1 and 8 every 3 weeks (w) for 6 or mom c cles (cy) in responding pts. The median number of courses was 3 ( -7). Four r pts were. excluded due to protocol violations. Demographic chara&ristics were: Median age 61 years(35-76), 66 male and 2 female, BCQG performance status rated: 0 in 20 pts, 1 in 40 and 2 in 8. Squamous cell carcinoma was diagnosed in 58%pts, adenoeareinoma in 22.5% and large cell in 19.5%. 40 pts were stage IV, 19 IIIB, 5 IIIA and 4 II. Response was evaluated according to WHO criteria in 48 pts who had me&&3 cy. Partial response was seen in 3 pts (6%) (%%CI=1.3-17.2). Stable disease was observed in 21 pts (43.7%) and progressive disease in 24 pts (50%). Median survival was 26.7~ and median time to progression 13.8~. 68 pts were evaluable for toxicity with 222 cy administered. Hematologieal tests wem. performed on days. 1, 8, 14, and 21. Gmde 3-4 neu~,leucopenra and anemra were meorded m 4.9%, 2:9% and 1 of the hematologrcal counts resPe&wely. Four pts requned hospitalization for drug-related infections. Grade 34 nausea and vomiting was seen in only 1 pt, and grade 3-4 alopecia in 3 pts. Severe neurotoxicity was not observed. Dose intensity was 20 mg/m2/w. In conclusion, the role of VRL in NSCL when used as single agent in a biweekly schedule should be regarded with caution.
