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A phase II study of navelbine® (NVB) and cisplatin (CDDP) in advanced non-small cell lung cancer stage IIIb-IV (NSCLC): interim results
s3.5
Abstracts
Between Apr. 1996 and Dec. 1997, 67 previously untreated NSCLC pts were enrolled. Patients: median age 61 (range: 36-75); male:female ratio 50:17; stage IIIB (12 pts>, IV (55 pts); ECOG performance status, O-l (59 pts), 2 (eight pts); adenocarcinoma (47 pts), squamous cell carcinoma (17 pts), poorly differentiated carcinoma (three pts). Oral EP consists of etoposide 50 mg/m2 in two divided doses PO Dl-21 and cisplatin 60 mg/m2 iv. Dl every 28 days. Results: Fifty-seven pts were evaluable. There was one CR, 18 PR (RR 33%; 95% CI 22.7-46.3%), 28 SD (49.1%) and 10 PD (17.5%). Median response duration was 27 weeks (13-53 weeks). Median survival (Kaplan-Meier) was 48 weeks (3-85 weeks) and l-year survival rate was 45.7%. Hematologic toxicities grade 3/4 consisted of; anemia 13.3%, leukopenia 6.6%, neutropenia 17.9% and thrombocytopenia 1.0%. Non-hematologic toxicities grade 3/4 included; vomiting 9.8%, stomatitis 16.4% and diarrhea 1.5%. Early treatment-related death occurred in two pts (3.0%) due to neutropenia complicated by infection. Conclusion: Oral EP is easy to administer and has moderate activity with tolerable toxicities in advanced NSCLC pts.
Combination of gemcitabine CC), ifosfamide (I) and vinorelbine (NJ for advanced non-small cell lung cancer (NSCLC): a phase II study Castellano D, Lianes P, Arcediano A, Garcia-Carbonero R, Paz-Ares L, CortCs-Funes H. Medical Oncology Department, Hospital Uniuersitatio Background: G,
‘12 de Octubre’,
Madrid,
Spain.
I and N have shown significant antitumor activity, as single agent and in combination, in NSCLC. The aim of this study was to assessthe toxicity and clinical profile of a non-cisplatin regimen (GIN) in chemonaive patients (pts) with advanced NSCLC. Materials and Methods: Treatment consisted of I 3 g/m2 day 1 (with Mesna); N 25 mg/m2 day 1 and 8; and G 1000 mg/m2 (first nine pts) or 1250 mg/m2 (subsequent pts) day 1 and 8, every 3 weeks. Pts with histologically confirmed advanced NSCLC, WHO PS O-2, measurable disease, and adequate hematological, hepatic and renal function, were eligible. Results: Fifty-one pts have been recruited with the following characteristics: median age 62 years (39-80); PS l/2: 26/11; squamous cell: 30, adenocarcinoma: 15 and others: 6; stage IV: 30 and IIIb: 18. A total of 182 courses have been given, with a median per pt of 3 (l-6). The relative dose-intensity of I, N and G were 95%, 86% and 86%, respectively. The major toxicity was hematological (% cycles): neutropenia G3-4: 41%, febrile neutropenia: 5.5%; thrombocytopenia G2-3: 10%; thrombocytosis: 37% and anemia G2: 11%. Non-hematological toxicity was mild: asthenia G2: 21%, constipation: 23% and alopecia G2: 60%. Among 40 pts currently evaluable for response, 1 CR (2.5%), 19 PR (47.5%), 14 SD (35%) and 6 PD (15%) were observed, for an overall response rate of 50% (95% CI: 31-72). There were three early deaths: atypical pneumonia (two pts) and non-thrombopenic hemoptisis (one pt). The median PFS and OS was 10.5 and 13.6 months, respectively. Conclusions: The GIN regimen has promising activity and manageable toxicity in advanced NSCLC pts. Mature QOL data will be presented.
VinoreIbine/gemcitabine in advanced non-small-cell lung cancer: a phase I trial Krajnik G, Wein W, Greil R, Marhold F, Mohn-Staudner A, Kummer F, Malayeri R, Zoechbauer-Mueller S, Huber H, Pirker R. Austrian Association for the Study of Lung Cancer (AASLC), Austria.
Department
for
Internal
Medicine
I, 1090
Vienna,
Vinorelbine/gemcitabine should be an interesting combination for palliative chemotherapy because these drugs have different mechanisms of action and good tolerability. Thus we initiated a phase I trial in advanced non-small-cell lung cancer in order to determine the maximum tolerated doses (MTD), the dose-limiting toxicities (DLT) and the most frequent side effects of this combination. Forty chemotherapy-naive patients were treated with different doses of vinorelbine/gemcitabine on days 1, 8 and 15, and this treatment cycle was repeated on day 29. Vinorelbine and gemcitabine were escalated from 10 to 30 mg/m’ and 600 to 1200 mg/m2, respectively. A total of 63 treatment cycles were administered and 27 patients received two treatment cycles. The MTD was established at vinorelbine 25 mg/m2 combined with 1200 mg/m2 gemcitabine. DLT were leukopenia plus thrombocytopenia (two patients) and mucositis (one patient). Frequent side effects were Ieukopenia, fever, nausea/vomiting, skin rashes and elevation of liver enzymes. The recommended phase II doses are 20-25 mg/m2 vinorelbine combined with 1000-1200 mg/m2 gemcitabine but myelosuppression will have to be carefully monitored. A phase II study of navelbine@ (NW) and cisplatin (CDDP) in advanced non-small cell lung cancer stage IIib-IV (NSCLC): interim results Depperman’ KM, Kurzeja’ A, Krause’ K, Miiller’ U, Le Bras2 F, Delchambre3 .I, Barbet-’ I, Lichey ’ J. Fachkrankenhaus jiir Lungenheilkunde und Thoraxchinagie, Karower Str.11, 13125 Berlin’; Pierre Fabre Pharma GmbH, Freiburg2; Institut de Recherche Pierre Fabre, Boulogne, France3 Objectice: NVB + CDDP is the only new combination de-
monstrating significant survival benefit compared to CDDP alone (SWOG study, ASCO 1998) and significant survival advantage after 6 years follow-up compared to standard CDDP based regimen (Le Chevalier, IASLC 1997). Materials and methods: To improve tolerance of such combination (especially CDDP tox.), a new schema has been designed: NVB 30 mg/m2 Dl + D8, CDDP 80 mg/m2 Dl every 3 weeks. After four courses: NVB 30 mg/m2 every 2 weeks as maintenance treatment until PD/excessive toxicity. Toxicity/tumor response was assessed according to WHO criteria every 3 and 6 weeks, respectively (PR + CR to be confirmed at least 4 weeks later). Results: 33 pts were included so far, 14 pts are assessable: 13 males, median age; 63.5 years (45-711, 12 pts stage IV (all 2 3 metastatic sites). PS: 0 (= 86%), 1 (= 7%), 2 (= 7%). Large-cell = 7, squamous-cell = 5, adenocarcinoma = 2. Neutropenia G3-4: 42% (shortly reversible without clinical consequences). No G3-4 infection or thrombocytopenia. G3-4 nausea: 8%, G3 alopecia: 9%. Lung oedema in one pt. No other G3-4 toxicities. Response so far (nine pts): 3 PR, 4 NC
S36
Abstracts
and 2 PD. Final analysis will be given at the meeting. Conclusion: This new schema seems to offer very safe first line treatment in bad prognostic NSCLC and could be considered a suitable validated treatment of stage BIB-IV NSCLC to ease out-patient administration. Gemcitabine and vinorelbine in advanced non-small cell lung canreT: a phase II trial VBzquez F, Baron FJ, Cueva JF, Candamio S, Calvo M, Irigoyen A, Huidobro C, Lopez R. Dept. of Medical Oncology C.H.U. Santiago, Background:
Spain.
Gemcitabine (G) and vinorelbine (V) are active drugs in non small cell lung cancer (NSCLC), both as single agents with 15% to 30% objective response. Aims: To evaluate activity of G + V in advanced NSCLC. Methods: G was given at dose of 1000 mg/m2 and V at 25 mg/m2. G and V were escalated if not evidence of toxicity. Between Jan 1997 and Nov 1997, 24 patients (pt) with advanced NSCLC started this combination all evaluable for toxicity. Characteristics of pt: males/females = 23/l; median age 61 years. (range 45-77); ECOG-PS O/1/2/3 = l/16/7; epid./adenoc./large cell = 15/5/14; stage IIIB/IV = 11/13. Results: 21 pt are currently evaluable for response with 33% overall response: one complete pathological response (obtained by bronchoscopy), six partial response, 28% stable disease, 38% progression. No toxic deaths or grade 4 WHO toxicities have occurred. For 235 weekly doses grade 3 anemia was observed in 2.5% and grade 3 neutropenia in 0.4%. The median number of cycles administered was three (range 1 to 7). G and V dose has been reduced in 15 pt and escalated in 15 pt. Median delivered dose-intensity G was 707 mg/m2 week and V 16.5 week. Conclusion: This weekly ambulatory n-e/m2 chemotherapy schedule without cisplatin has a good response with low toxicity and allows us to add a third drug. Salvage treatment with paclitaxel and gemcitabine for patients with non-small cell lung cancer alter cisplatin- or docetaxelbased chemotherapy: a multicenter phase II study Androulakis N, Kourousis Ch, Kakolyris S, Tzannes S, Papadakis E, Papadimitriou Ch, Geroyanni A, Georgopoulou Th, Dimopoulou I, Souklakos J, Tzianni V, Apostolaki F, Kotsakis A, Vardakis N, Kalikaki T, Hatzidaki D, Georgoulias V. From the Greek Cooperative Group for Lung Cancer, Greece. Purpose: To evaluate the tolerance and efficacy of paclitaxel and gemcitabine combination in patients with advanced nonsmall cell lung cancer (NSCLC) who relapsed or progressed after cisplatin- or/and docetaxel-based chemotherapy. Patients and Methods: Between January 1996 and June 1997,49 patients (median age 60.5 years) with measurable NSCLC who progressed or failed first-line cisplatin- or/and docetaxel-based chemotherapy were enrolled. Prior chemotherapy was cisplatin-based with (n = 20; 41%) or without (n = 22; 45%) docetaxel and docetaxel-vinorelbine (n = 7; 14%). The median interval between first- and second-line chemotherapy was 5.2 weeks (range 4-76). Forty patients (80%) had PS (WHO) O-l, 41 (84%) had stage IV disease and histology was adenocarci-
noma in 22 (45%). Patients received gemcitabine (900 mg/m2) on days 1 and 8 and paclitaxel (175 mg/m2) on day 8 with appropriate premeditation, every 3 weeks. Granulocyte colony-stimulating factor support (150 pg/m2, sc.) was given prophylacticlly on days 9-15. Results: CR was achieved in one (2%) and PR in eight (16.3%) patients (overall response rate 18.3%; 95% C.I. 4.3-23.6%x 14 patients (28.6%) had SD and 26 (53.1%) PD. Six objective responses (35.3%) were observed in 17 patients who responded to first-line chemotherapy. The overall median duration of response was 7 months, the median time to tumor progression 8 months and the median survival 10 months. The l-year survival was 37%. Grade 3/4 (WHO) neutropenia occurred in six (12%) patients and grade 4 thrombocytopenia in one (2%). There was no treatment-related death. Grade 2 and 3 neurotoxicity occurred in 12 (24%) and four (8%) patients, respectively, grade 2/3 asthenia in 25 (51%), mild allergic reactions in five (lo%), flu-like syndrome in seven (14%) and grade 2 oedema in four (8%). Conclusions: The paclitaxel-gemcitabine combination is an outpatient, well tolerated and relatively active salvage regimen in patients with advanced NSCLC; this regimen merits further investigation in patients who relapse as an initial response to the front-line chemotherapy. Second-line treatment of non-small cell lung carcinomas with vinorelbine and ifosfamide: preliminary results of a phase II trial of the Greek Cooperative Group for Lung Cancer Papadakis E, Kourousis Ch, Androulakis N, Agelaki S, Apostolopoulou F, Palamidas F, Rapti A, Sarra E, Tziani V, Bania E, Agelidou A, Gianakakis Th, Kandilis K, Adravanis A, Apostolaki F, Georgoulias V. The Greek Cooperative Group for Lung Cancer, Dept. Hospital of Heraklion,
Medical Oncology, Universiv 71110 Heraklion, Crete, Greece.
of
General
Purpose: To evaluate the tolerance and efficacy of the vinorelbine (VRB) and ifosfamide (IFOJ combination as second line treatment in patients with refractory or relapsed non-small-cell lung cancer (NSCLC). Patients and Methods: Twenty-three patients with bidimensionally measurable and histologically confirmed NSCLC who failed or relapsed after first-line chemotherapy were enrolled. Their median age was 61 years (range, 27-751, 21 were male, eight had stage IIIB and 15 stage IV disease, and their performance status (WHO) was O-l in 12 (52%) and 2 in 11 (48%). Histology was adenocarcinoma in four patients (17%) and non-adenocarcinema in 19 (83%). Patients received VRB (25 mg/m’ over a 30-min i.v. infusion, on day 1 and 8) and IF0 (1.6 g/m2 over a l-h i.v. infusion on days 8-10) with mesna uroprotection. The cycles were repeated every 3 weeks. Results: All patients were evaluable for toxicity and 17 for response (six too early). So far, 64 cycles were administered with a median of two cycles/patient (range, l-6). Fifteen (23%) cycles were delayed mostly for reasons unrelated to treatment or the disease (one cycle was delayed because of toxicity). Patients received 95% of the protocol planned dose for NRB (range, 444100%) and IF0 (range, 533100%). Two patients (9%) developed grade 3 neutropenia, three (13%) grade 2/3 neurotoxicity, and tight (35%) grade 2 asthcnia; febrile neutropenia occurred in three
Abstracts
Between Apr. 1996 and Dec. 1997, 67 previously untreated NSCLC pts were enrolled. Patients: median age 61 (range: 36-75); male:female ratio 50:17; stage IIIB (12 pts>, IV (55 pts); ECOG performance status, O-l (59 pts), 2 (eight pts); adenocarcinoma (47 pts), squamous cell carcinoma (17 pts), poorly differentiated carcinoma (three pts). Oral EP consists of etoposide 50 mg/m2 in two divided doses PO Dl-21 and cisplatin 60 mg/m2 iv. Dl every 28 days. Results: Fifty-seven pts were evaluable. There was one CR, 18 PR (RR 33%; 95% CI 22.7-46.3%), 28 SD (49.1%) and 10 PD (17.5%). Median response duration was 27 weeks (13-53 weeks). Median survival (Kaplan-Meier) was 48 weeks (3-85 weeks) and l-year survival rate was 45.7%. Hematologic toxicities grade 3/4 consisted of; anemia 13.3%, leukopenia 6.6%, neutropenia 17.9% and thrombocytopenia 1.0%. Non-hematologic toxicities grade 3/4 included; vomiting 9.8%, stomatitis 16.4% and diarrhea 1.5%. Early treatment-related death occurred in two pts (3.0%) due to neutropenia complicated by infection. Conclusion: Oral EP is easy to administer and has moderate activity with tolerable toxicities in advanced NSCLC pts.
Combination of gemcitabine CC), ifosfamide (I) and vinorelbine (NJ for advanced non-small cell lung cancer (NSCLC): a phase II study Castellano D, Lianes P, Arcediano A, Garcia-Carbonero R, Paz-Ares L, CortCs-Funes H. Medical Oncology Department, Hospital Uniuersitatio Background: G,
‘12 de Octubre’,
Madrid,
Spain.
I and N have shown significant antitumor activity, as single agent and in combination, in NSCLC. The aim of this study was to assessthe toxicity and clinical profile of a non-cisplatin regimen (GIN) in chemonaive patients (pts) with advanced NSCLC. Materials and Methods: Treatment consisted of I 3 g/m2 day 1 (with Mesna); N 25 mg/m2 day 1 and 8; and G 1000 mg/m2 (first nine pts) or 1250 mg/m2 (subsequent pts) day 1 and 8, every 3 weeks. Pts with histologically confirmed advanced NSCLC, WHO PS O-2, measurable disease, and adequate hematological, hepatic and renal function, were eligible. Results: Fifty-one pts have been recruited with the following characteristics: median age 62 years (39-80); PS l/2: 26/11; squamous cell: 30, adenocarcinoma: 15 and others: 6; stage IV: 30 and IIIb: 18. A total of 182 courses have been given, with a median per pt of 3 (l-6). The relative dose-intensity of I, N and G were 95%, 86% and 86%, respectively. The major toxicity was hematological (% cycles): neutropenia G3-4: 41%, febrile neutropenia: 5.5%; thrombocytopenia G2-3: 10%; thrombocytosis: 37% and anemia G2: 11%. Non-hematological toxicity was mild: asthenia G2: 21%, constipation: 23% and alopecia G2: 60%. Among 40 pts currently evaluable for response, 1 CR (2.5%), 19 PR (47.5%), 14 SD (35%) and 6 PD (15%) were observed, for an overall response rate of 50% (95% CI: 31-72). There were three early deaths: atypical pneumonia (two pts) and non-thrombopenic hemoptisis (one pt). The median PFS and OS was 10.5 and 13.6 months, respectively. Conclusions: The GIN regimen has promising activity and manageable toxicity in advanced NSCLC pts. Mature QOL data will be presented.
VinoreIbine/gemcitabine in advanced non-small-cell lung cancer: a phase I trial Krajnik G, Wein W, Greil R, Marhold F, Mohn-Staudner A, Kummer F, Malayeri R, Zoechbauer-Mueller S, Huber H, Pirker R. Austrian Association for the Study of Lung Cancer (AASLC), Austria.
Department
for
Internal
Medicine
I, 1090
Vienna,
Vinorelbine/gemcitabine should be an interesting combination for palliative chemotherapy because these drugs have different mechanisms of action and good tolerability. Thus we initiated a phase I trial in advanced non-small-cell lung cancer in order to determine the maximum tolerated doses (MTD), the dose-limiting toxicities (DLT) and the most frequent side effects of this combination. Forty chemotherapy-naive patients were treated with different doses of vinorelbine/gemcitabine on days 1, 8 and 15, and this treatment cycle was repeated on day 29. Vinorelbine and gemcitabine were escalated from 10 to 30 mg/m’ and 600 to 1200 mg/m2, respectively. A total of 63 treatment cycles were administered and 27 patients received two treatment cycles. The MTD was established at vinorelbine 25 mg/m2 combined with 1200 mg/m2 gemcitabine. DLT were leukopenia plus thrombocytopenia (two patients) and mucositis (one patient). Frequent side effects were Ieukopenia, fever, nausea/vomiting, skin rashes and elevation of liver enzymes. The recommended phase II doses are 20-25 mg/m2 vinorelbine combined with 1000-1200 mg/m2 gemcitabine but myelosuppression will have to be carefully monitored. A phase II study of navelbine@ (NW) and cisplatin (CDDP) in advanced non-small cell lung cancer stage IIib-IV (NSCLC): interim results Depperman’ KM, Kurzeja’ A, Krause’ K, Miiller’ U, Le Bras2 F, Delchambre3 .I, Barbet-’ I, Lichey ’ J. Fachkrankenhaus jiir Lungenheilkunde und Thoraxchinagie, Karower Str.11, 13125 Berlin’; Pierre Fabre Pharma GmbH, Freiburg2; Institut de Recherche Pierre Fabre, Boulogne, France3 Objectice: NVB + CDDP is the only new combination de-
monstrating significant survival benefit compared to CDDP alone (SWOG study, ASCO 1998) and significant survival advantage after 6 years follow-up compared to standard CDDP based regimen (Le Chevalier, IASLC 1997). Materials and methods: To improve tolerance of such combination (especially CDDP tox.), a new schema has been designed: NVB 30 mg/m2 Dl + D8, CDDP 80 mg/m2 Dl every 3 weeks. After four courses: NVB 30 mg/m2 every 2 weeks as maintenance treatment until PD/excessive toxicity. Toxicity/tumor response was assessed according to WHO criteria every 3 and 6 weeks, respectively (PR + CR to be confirmed at least 4 weeks later). Results: 33 pts were included so far, 14 pts are assessable: 13 males, median age; 63.5 years (45-711, 12 pts stage IV (all 2 3 metastatic sites). PS: 0 (= 86%), 1 (= 7%), 2 (= 7%). Large-cell = 7, squamous-cell = 5, adenocarcinoma = 2. Neutropenia G3-4: 42% (shortly reversible without clinical consequences). No G3-4 infection or thrombocytopenia. G3-4 nausea: 8%, G3 alopecia: 9%. Lung oedema in one pt. No other G3-4 toxicities. Response so far (nine pts): 3 PR, 4 NC
S36
Abstracts
and 2 PD. Final analysis will be given at the meeting. Conclusion: This new schema seems to offer very safe first line treatment in bad prognostic NSCLC and could be considered a suitable validated treatment of stage BIB-IV NSCLC to ease out-patient administration. Gemcitabine and vinorelbine in advanced non-small cell lung canreT: a phase II trial VBzquez F, Baron FJ, Cueva JF, Candamio S, Calvo M, Irigoyen A, Huidobro C, Lopez R. Dept. of Medical Oncology C.H.U. Santiago, Background:
Spain.
Gemcitabine (G) and vinorelbine (V) are active drugs in non small cell lung cancer (NSCLC), both as single agents with 15% to 30% objective response. Aims: To evaluate activity of G + V in advanced NSCLC. Methods: G was given at dose of 1000 mg/m2 and V at 25 mg/m2. G and V were escalated if not evidence of toxicity. Between Jan 1997 and Nov 1997, 24 patients (pt) with advanced NSCLC started this combination all evaluable for toxicity. Characteristics of pt: males/females = 23/l; median age 61 years. (range 45-77); ECOG-PS O/1/2/3 = l/16/7; epid./adenoc./large cell = 15/5/14; stage IIIB/IV = 11/13. Results: 21 pt are currently evaluable for response with 33% overall response: one complete pathological response (obtained by bronchoscopy), six partial response, 28% stable disease, 38% progression. No toxic deaths or grade 4 WHO toxicities have occurred. For 235 weekly doses grade 3 anemia was observed in 2.5% and grade 3 neutropenia in 0.4%. The median number of cycles administered was three (range 1 to 7). G and V dose has been reduced in 15 pt and escalated in 15 pt. Median delivered dose-intensity G was 707 mg/m2 week and V 16.5 week. Conclusion: This weekly ambulatory n-e/m2 chemotherapy schedule without cisplatin has a good response with low toxicity and allows us to add a third drug. Salvage treatment with paclitaxel and gemcitabine for patients with non-small cell lung cancer alter cisplatin- or docetaxelbased chemotherapy: a multicenter phase II study Androulakis N, Kourousis Ch, Kakolyris S, Tzannes S, Papadakis E, Papadimitriou Ch, Geroyanni A, Georgopoulou Th, Dimopoulou I, Souklakos J, Tzianni V, Apostolaki F, Kotsakis A, Vardakis N, Kalikaki T, Hatzidaki D, Georgoulias V. From the Greek Cooperative Group for Lung Cancer, Greece. Purpose: To evaluate the tolerance and efficacy of paclitaxel and gemcitabine combination in patients with advanced nonsmall cell lung cancer (NSCLC) who relapsed or progressed after cisplatin- or/and docetaxel-based chemotherapy. Patients and Methods: Between January 1996 and June 1997,49 patients (median age 60.5 years) with measurable NSCLC who progressed or failed first-line cisplatin- or/and docetaxel-based chemotherapy were enrolled. Prior chemotherapy was cisplatin-based with (n = 20; 41%) or without (n = 22; 45%) docetaxel and docetaxel-vinorelbine (n = 7; 14%). The median interval between first- and second-line chemotherapy was 5.2 weeks (range 4-76). Forty patients (80%) had PS (WHO) O-l, 41 (84%) had stage IV disease and histology was adenocarci-
noma in 22 (45%). Patients received gemcitabine (900 mg/m2) on days 1 and 8 and paclitaxel (175 mg/m2) on day 8 with appropriate premeditation, every 3 weeks. Granulocyte colony-stimulating factor support (150 pg/m2, sc.) was given prophylacticlly on days 9-15. Results: CR was achieved in one (2%) and PR in eight (16.3%) patients (overall response rate 18.3%; 95% C.I. 4.3-23.6%x 14 patients (28.6%) had SD and 26 (53.1%) PD. Six objective responses (35.3%) were observed in 17 patients who responded to first-line chemotherapy. The overall median duration of response was 7 months, the median time to tumor progression 8 months and the median survival 10 months. The l-year survival was 37%. Grade 3/4 (WHO) neutropenia occurred in six (12%) patients and grade 4 thrombocytopenia in one (2%). There was no treatment-related death. Grade 2 and 3 neurotoxicity occurred in 12 (24%) and four (8%) patients, respectively, grade 2/3 asthenia in 25 (51%), mild allergic reactions in five (lo%), flu-like syndrome in seven (14%) and grade 2 oedema in four (8%). Conclusions: The paclitaxel-gemcitabine combination is an outpatient, well tolerated and relatively active salvage regimen in patients with advanced NSCLC; this regimen merits further investigation in patients who relapse as an initial response to the front-line chemotherapy. Second-line treatment of non-small cell lung carcinomas with vinorelbine and ifosfamide: preliminary results of a phase II trial of the Greek Cooperative Group for Lung Cancer Papadakis E, Kourousis Ch, Androulakis N, Agelaki S, Apostolopoulou F, Palamidas F, Rapti A, Sarra E, Tziani V, Bania E, Agelidou A, Gianakakis Th, Kandilis K, Adravanis A, Apostolaki F, Georgoulias V. The Greek Cooperative Group for Lung Cancer, Dept. Hospital of Heraklion,
Medical Oncology, Universiv 71110 Heraklion, Crete, Greece.
of
General
Purpose: To evaluate the tolerance and efficacy of the vinorelbine (VRB) and ifosfamide (IFOJ combination as second line treatment in patients with refractory or relapsed non-small-cell lung cancer (NSCLC). Patients and Methods: Twenty-three patients with bidimensionally measurable and histologically confirmed NSCLC who failed or relapsed after first-line chemotherapy were enrolled. Their median age was 61 years (range, 27-751, 21 were male, eight had stage IIIB and 15 stage IV disease, and their performance status (WHO) was O-l in 12 (52%) and 2 in 11 (48%). Histology was adenocarcinoma in four patients (17%) and non-adenocarcinema in 19 (83%). Patients received VRB (25 mg/m’ over a 30-min i.v. infusion, on day 1 and 8) and IF0 (1.6 g/m2 over a l-h i.v. infusion on days 8-10) with mesna uroprotection. The cycles were repeated every 3 weeks. Results: All patients were evaluable for toxicity and 17 for response (six too early). So far, 64 cycles were administered with a median of two cycles/patient (range, l-6). Fifteen (23%) cycles were delayed mostly for reasons unrelated to treatment or the disease (one cycle was delayed because of toxicity). Patients received 95% of the protocol planned dose for NRB (range, 444100%) and IF0 (range, 533100%). Two patients (9%) developed grade 3 neutropenia, three (13%) grade 2/3 neurotoxicity, and tight (35%) grade 2 asthcnia; febrile neutropenia occurred in three