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Vinorelbine (Navelbine)-A new agent for the treatment of non-small cell lung cancer: A summary
312
Abstracts
/Lung
Cancer
Park, NC; Pierre Fabre Mcdicament, Paris, France) in current and future trials of adjuvant and nwadjuvant treatment of non-small cell lung cancer. In locally advanced, unresectable disease, the lo-week regimen is cisplatin 100 mg/ml during weeks I and 5, vinorelbine 30 mg/m’ weekly for 5 weeks with B 50% dose reduction planned for week 2 only, and accelerated fractionation thoracic irradistion during weeks 7 to IO (30 fractions of 2 Gy in 4 weeks, once daily during waks 7 and 8, and twcc daily during weeks 9 and IO). Preliminary data on I7 patients who have completed treatment to date show it has been well tolerated. with only four cases of grade 3 nonhematologic toxicities. Favorable results from combined therapy with cisplatin and vinorelbine in advanced disease have led the National Cancer Institute of Canada Clinical Trials Group to consider testing adjuvant cisplatin and vinorelbinc m completely resected non-small cell lung cancer. Surgically staged patients with T2, NO and Tl-2NI tumors will be stratified according to nodal status and presence or absence of ras oneogene mutations in resected tumor DNA. Patients will be randomized to observation or a l6- week trial of adjuvant chemotherapy with cisplstin 50 mg/m’ days I and 8 every 4 weeks during the I6 weeks, and vinorelbme 30 mglrnl weekly for I6 weeks. All resected tumors till be banked for further correlative studies to identify a clinically meaningful panel of molecular prognostic markers.
Oral vinorelbine cell lung cancer:
(Navelbine) in the treatment A preliminary report
of advanced
non-small
Vokes EE, Rosenberg R, Jahanzeb M. Craig J, Gralla R, Belani C et al. Universi+’ of Chicago. 5841 S Masyland Ave. Chicago. IL 60637-1475. Semin Onwl. 1994;21:Suppl. 10:35-41. Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France) is a novel semisynthetic vinca alkaloid with antitumor activity in non-small cell lung cancer. An oral preparation of this drug is under investigation and was tested in a multicenter phase II study in patients with stage IV measurable or evaluable non-small cell lung cancer. The initial vinorelbine dose was 100 mglm’lwk (80 mglm’lwk for patients with prior radiotherapy). Following an initial 37% incidence of grade 3 or 4 ncutropenia, the dose was reduced by 40 “g/dose. Nausea, vomiting, diarrhea, and muwsitis were other frequently observed toxicities. A preliminary analysis indicated a response rate of 14%. suggesting activity of this drug when administered orally.
A three-arm trial of vinorelbine (Navelbioe) plus cisplatin, vindesine plus cisplatin, and single-agent vinorelbine in tbe treatment of nonsmall cell lung cancer: An expanded analysis Le Chevalier T, Pujol J-L, Douillard J-Y, Alberola V, Monnier A, Riviere A et al. Con&e de Parhologie Thoracique. Inrtihrr Gusrove Rous+x 94805 Wiejuf Cedex. Scmin Oncol 1994;2l:Suppl 10:28-34. Phase II studies have demonstrated that vinorelbine (Navclbine; Bumoughs Wellcoma Co, Research Triangle Park, NC, Pierre Fabre Medicament, Paris, France) alone or in combination with cisplatin has promising activity against non-small cell lung cancer (NSCLC). On the basis of these preliminary trials, a phase III study was designed to compare intravenous vinorelbine (30 mp/m’ weekly) plus cisplatin (120 mg/m’ on day 1 and day 29 and then evely 6 weeks) with vindcsine (3 mg/m’ weekly for 6 weeks and then every 2 weeks) plus cisplatin, and to evaluate whether the best of these regimens afforded a survival benefit compared with intravenous vinorelbine alone, an outpatient regimen. This report presents an expanded analysis of data from this previously published study. Six hundred hvelve patients were enrolled in this trial: 206 in the vinorelbine plus cisplatin arm, 200 in the vindcsinc plus cisplatin group, and 206 in the single-agent vinorelbinc arm. The vinorelbinc plus cisplatin regimen was superior to the other hvo arms of the study in objective response rate (30% v 19% for vindesine plus cisplatin [p = .02] and 14% for vinorelbine alone [p = .OOl]), median survival duration (40 weeks v 32 weeks for vindesine plus cisplatin and 31 weeks forvinorelbincalone), and I-year survival rate (35% ~27% for vindesine plus cisplatin and 30% for vinorelbine alone). An adjusted log-rank test provided a signiticant advantage for vinorelbinc plus cisplatin when compared with vindesine plus cisplatin (p = .04) and with vinorelbine alone (F’ = .02). The major difference in survival between the two cisplatin+ontaining regimens occurred in patients with mctastatic (stage IV) NSCLC. The incidence of granulocytopenia was significantly higher in the vinorelbine plus cisplatin arm compared with the other
12 (1995)
265-329
hvo treatment groups, but ncurotoxicity was significantly more frequent in the vindcsine plus cisplstin group. The results of this study indicate that the combination of vinorelbine plus cisplatin is a viable treatment option for patients with NSCLC and may provide advantages compared with other commonly used regimens.
Vmorelbine (Navelbine) -A new agent for tbe treatment cell lungcaocer: A summary
of non-small
Coltman CA Jr. Deparbnen~ o/Medicine. San Anlonio Cancerlnsti~u~e, Vniv 01 Texas Heawl Science Center: 8122 Dafapoinr Dr. San Antonio. TX 78229. Semin Oncol 1994;2l:Suppl l&l-3. A large body of preclinical and clinical data concerning the new semisynthetic vinca alkaloid vinorelbinc (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicamcnt, Paris, France) are now available. At both the cellular and clinical levels, this drug shows reduced neurotoxicity compared with other vines alkaloids. In phase III clinical trials of patients with advanced non-small cell lungcanccr (NSCLC), treatment with the combination of vinorelbine end cisplatin resulted in survival advantages greater than those achieved by vindcsinc plus cisplatin. The median survival durations of patients receiving single-agent vinorelbine were comparable with those of pticnts treated with vindcsinc plus cisplatin, and greater than those of patients treated with 5fluorouracil and Ieucovorin. The dose-limiting toxicity of vinorclbine, gmnulocytolzenia, was transient and seldom resulted in hospitnliition. Trestmcnt with vinorelbinc did not result in negative effects of patient quality of life. Vinorelbinc is now being actively investigated in combination and multimodality regimens in patients with various stagea of NSCLC. New strategies to avoid vinorelbine- related granulocytopenia are also being developed. Vinorelbinecontaining regimens hold the promise of providing effective, well-tolerated treatment for patients with NSCLC.
Drug delivery analysis of tbe Canadian cell lung cancer
multicenter
trial in nonsmall-
Murray N, Coppin C, Coldman A, P&r J, Rapp E. Brifish Columbia Cancer Agency, 600 W IOh Ave. Vancouver BC VSZ 4E6. J Clin Oncol 1994;12:2333-9. Purpose: The Canadian multicenter trial for advanced non-smallcell lung cancer (NSCLC) reported survival benefit for chemotherapy when best supportive care was compared with vindesine-cisplatin (VP) and the combination of cyclophosphamidc, doxorubicin, and cisplatin (CAP). We examined received drug delivcly to document dose-intensity (DI) and total dose of drugs given to various groups in this patient population. Patients and Merhods: Plots of cumulatively received chemotherapy against time were used to evaluate drug delivery by regimen, major prognostic factors, and response status. Resrrfts: Individual CAP patients show a narrow range of wived DI, with the median similar to protocol. Drug dclivcty analysis expxed a tide range of received DI for both drugs in the more intensive VP regimen, and the median received DI was below protocol. The median received DI for cisplatin was still higher for VP than CAP, but only during the first 8 weeks of protocol treatment (20 v 10 mg/m’/wk), thereat?er, the ongoing received cisplatin DI ws the same (I 0 mg/m’/ wk). The median received DI for cisplatin in each regimen was not influenced by stage, performance status, prior weight loss, sex, or response status. VP-treated patients received B higher total dose of cisplatin than CAP patients (median, 255 mg/ml v 112.5 mp/m’; P < .OOOl). Median cisplstin total dose was similar for patients with a chemotherapy response or stable disease and threefold greater than for patients with progressive disease for both regimens. Although patients with chemotherapy response and stable disease had similar survival outwmcs for both CAP and VP, the VP regimen had a higher proportion of patients without progressive disease (P = .004), which resulted in an overall survival advantage (P = .Ol). Conclusion: The major prognostic factors for advanced NSCLC do not exert their influence on outcome by affecting deliverable chemotherapy DI. Regimen and treatment response determined total dose. Because stable disease patients usually outnumber responding patients in advanced NSCLC trials, eontmlled studies should be performed that allow asscssmcnt of the impact of total reccwed dose on outcome according to response status.
Abstracts
/Lung
Cancer
Park, NC; Pierre Fabre Mcdicament, Paris, France) in current and future trials of adjuvant and nwadjuvant treatment of non-small cell lung cancer. In locally advanced, unresectable disease, the lo-week regimen is cisplatin 100 mg/ml during weeks I and 5, vinorelbine 30 mg/m’ weekly for 5 weeks with B 50% dose reduction planned for week 2 only, and accelerated fractionation thoracic irradistion during weeks 7 to IO (30 fractions of 2 Gy in 4 weeks, once daily during waks 7 and 8, and twcc daily during weeks 9 and IO). Preliminary data on I7 patients who have completed treatment to date show it has been well tolerated. with only four cases of grade 3 nonhematologic toxicities. Favorable results from combined therapy with cisplatin and vinorelbine in advanced disease have led the National Cancer Institute of Canada Clinical Trials Group to consider testing adjuvant cisplatin and vinorelbinc m completely resected non-small cell lung cancer. Surgically staged patients with T2, NO and Tl-2NI tumors will be stratified according to nodal status and presence or absence of ras oneogene mutations in resected tumor DNA. Patients will be randomized to observation or a l6- week trial of adjuvant chemotherapy with cisplstin 50 mg/m’ days I and 8 every 4 weeks during the I6 weeks, and vinorelbme 30 mglrnl weekly for I6 weeks. All resected tumors till be banked for further correlative studies to identify a clinically meaningful panel of molecular prognostic markers.
Oral vinorelbine cell lung cancer:
(Navelbine) in the treatment A preliminary report
of advanced
non-small
Vokes EE, Rosenberg R, Jahanzeb M. Craig J, Gralla R, Belani C et al. Universi+’ of Chicago. 5841 S Masyland Ave. Chicago. IL 60637-1475. Semin Onwl. 1994;21:Suppl. 10:35-41. Vinorelbine (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicament, Paris, France) is a novel semisynthetic vinca alkaloid with antitumor activity in non-small cell lung cancer. An oral preparation of this drug is under investigation and was tested in a multicenter phase II study in patients with stage IV measurable or evaluable non-small cell lung cancer. The initial vinorelbine dose was 100 mglm’lwk (80 mglm’lwk for patients with prior radiotherapy). Following an initial 37% incidence of grade 3 or 4 ncutropenia, the dose was reduced by 40 “g/dose. Nausea, vomiting, diarrhea, and muwsitis were other frequently observed toxicities. A preliminary analysis indicated a response rate of 14%. suggesting activity of this drug when administered orally.
A three-arm trial of vinorelbine (Navelbioe) plus cisplatin, vindesine plus cisplatin, and single-agent vinorelbine in tbe treatment of nonsmall cell lung cancer: An expanded analysis Le Chevalier T, Pujol J-L, Douillard J-Y, Alberola V, Monnier A, Riviere A et al. Con&e de Parhologie Thoracique. Inrtihrr Gusrove Rous+x 94805 Wiejuf Cedex. Scmin Oncol 1994;2l:Suppl 10:28-34. Phase II studies have demonstrated that vinorelbine (Navclbine; Bumoughs Wellcoma Co, Research Triangle Park, NC, Pierre Fabre Medicament, Paris, France) alone or in combination with cisplatin has promising activity against non-small cell lung cancer (NSCLC). On the basis of these preliminary trials, a phase III study was designed to compare intravenous vinorelbine (30 mp/m’ weekly) plus cisplatin (120 mg/m’ on day 1 and day 29 and then evely 6 weeks) with vindcsine (3 mg/m’ weekly for 6 weeks and then every 2 weeks) plus cisplatin, and to evaluate whether the best of these regimens afforded a survival benefit compared with intravenous vinorelbine alone, an outpatient regimen. This report presents an expanded analysis of data from this previously published study. Six hundred hvelve patients were enrolled in this trial: 206 in the vinorelbine plus cisplatin arm, 200 in the vindcsinc plus cisplatin group, and 206 in the single-agent vinorelbinc arm. The vinorelbinc plus cisplatin regimen was superior to the other hvo arms of the study in objective response rate (30% v 19% for vindesine plus cisplatin [p = .02] and 14% for vinorelbine alone [p = .OOl]), median survival duration (40 weeks v 32 weeks for vindesine plus cisplatin and 31 weeks forvinorelbincalone), and I-year survival rate (35% ~27% for vindesine plus cisplatin and 30% for vinorelbine alone). An adjusted log-rank test provided a signiticant advantage for vinorelbinc plus cisplatin when compared with vindesine plus cisplatin (p = .04) and with vinorelbine alone (F’ = .02). The major difference in survival between the two cisplatin+ontaining regimens occurred in patients with mctastatic (stage IV) NSCLC. The incidence of granulocytopenia was significantly higher in the vinorelbine plus cisplatin arm compared with the other
12 (1995)
265-329
hvo treatment groups, but ncurotoxicity was significantly more frequent in the vindcsine plus cisplstin group. The results of this study indicate that the combination of vinorelbine plus cisplatin is a viable treatment option for patients with NSCLC and may provide advantages compared with other commonly used regimens.
Vmorelbine (Navelbine) -A new agent for tbe treatment cell lungcaocer: A summary
of non-small
Coltman CA Jr. Deparbnen~ o/Medicine. San Anlonio Cancerlnsti~u~e, Vniv 01 Texas Heawl Science Center: 8122 Dafapoinr Dr. San Antonio. TX 78229. Semin Oncol 1994;2l:Suppl l&l-3. A large body of preclinical and clinical data concerning the new semisynthetic vinca alkaloid vinorelbinc (Navelbine; Burroughs Wellcome Co, Research Triangle Park, NC; Pierre Fabre Medicamcnt, Paris, France) are now available. At both the cellular and clinical levels, this drug shows reduced neurotoxicity compared with other vines alkaloids. In phase III clinical trials of patients with advanced non-small cell lungcanccr (NSCLC), treatment with the combination of vinorelbine end cisplatin resulted in survival advantages greater than those achieved by vindcsinc plus cisplatin. The median survival durations of patients receiving single-agent vinorelbine were comparable with those of pticnts treated with vindcsinc plus cisplatin, and greater than those of patients treated with 5fluorouracil and Ieucovorin. The dose-limiting toxicity of vinorclbine, gmnulocytolzenia, was transient and seldom resulted in hospitnliition. Trestmcnt with vinorelbinc did not result in negative effects of patient quality of life. Vinorelbinc is now being actively investigated in combination and multimodality regimens in patients with various stagea of NSCLC. New strategies to avoid vinorelbine- related granulocytopenia are also being developed. Vinorelbinecontaining regimens hold the promise of providing effective, well-tolerated treatment for patients with NSCLC.
Drug delivery analysis of tbe Canadian cell lung cancer
multicenter
trial in nonsmall-
Murray N, Coppin C, Coldman A, P&r J, Rapp E. Brifish Columbia Cancer Agency, 600 W IOh Ave. Vancouver BC VSZ 4E6. J Clin Oncol 1994;12:2333-9. Purpose: The Canadian multicenter trial for advanced non-smallcell lung cancer (NSCLC) reported survival benefit for chemotherapy when best supportive care was compared with vindesine-cisplatin (VP) and the combination of cyclophosphamidc, doxorubicin, and cisplatin (CAP). We examined received drug delivcly to document dose-intensity (DI) and total dose of drugs given to various groups in this patient population. Patients and Merhods: Plots of cumulatively received chemotherapy against time were used to evaluate drug delivery by regimen, major prognostic factors, and response status. Resrrfts: Individual CAP patients show a narrow range of wived DI, with the median similar to protocol. Drug dclivcty analysis expxed a tide range of received DI for both drugs in the more intensive VP regimen, and the median received DI was below protocol. The median received DI for cisplatin was still higher for VP than CAP, but only during the first 8 weeks of protocol treatment (20 v 10 mg/m’/wk), thereat?er, the ongoing received cisplatin DI ws the same (I 0 mg/m’/ wk). The median received DI for cisplatin in each regimen was not influenced by stage, performance status, prior weight loss, sex, or response status. VP-treated patients received B higher total dose of cisplatin than CAP patients (median, 255 mg/ml v 112.5 mp/m’; P < .OOOl). Median cisplstin total dose was similar for patients with a chemotherapy response or stable disease and threefold greater than for patients with progressive disease for both regimens. Although patients with chemotherapy response and stable disease had similar survival outwmcs for both CAP and VP, the VP regimen had a higher proportion of patients without progressive disease (P = .004), which resulted in an overall survival advantage (P = .Ol). Conclusion: The major prognostic factors for advanced NSCLC do not exert their influence on outcome by affecting deliverable chemotherapy DI. Regimen and treatment response determined total dose. Because stable disease patients usually outnumber responding patients in advanced NSCLC trials, eontmlled studies should be performed that allow asscssmcnt of the impact of total reccwed dose on outcome according to response status.