Abstract
The present study was aimed at defining the antitumour activity of the cisplatin-paclitaxel-topotecan (CPT) weekly administration with G-CSF support in chemo-naive SCLC patients with extensive disease (ED-SCLC). Chemonaive ED-SCLC patients received cisplatin 40 mg/m2, paclitaxel 85 mg/m2, and topotecan 2.25 mg/m2weekly, with G-CSF (5 μg/kg days 3–5) support, for a maximum of 12 weeks. 37 patients were treated, for a total of 348 cycles delivered. 8 complete responses (22%) and 22 partial responses (59%) were recorded, giving an 81% [95% CI = 65–92%] ORR. At a 13-month (range, 4–26) median follow-up, median progression-free and overall survival were 8 months and 12.5 months, with 1-year and 2-year projected survivals of 55% and 21%, respectively. No toxic deaths occurred. Grade 4 neutropenia and thrombocytopenia occurred in 6 and 3 patients, respectively. Only one case of neutropenic sepsis was recorded, while haemorrhagic thrombocytopenia was never observed. Diarrhoea, paraesthesias and fatigue were the main nonhaematologic toxicities being severe in 6, 2 and 10 patients, respectively. The weekly CPT combination with G-CSF support represents a well tolerated therapeutic approach in chemo-naive ED-SCLC patients. The activity rate seems at least similar to that achievable with the standard front-line approaches. © 2001 Cancer Research Campaign http://www.bjcancer.com
Similar content being viewed by others
Article PDF
Change history
16 November 2011
This paper was modified 12 months after initial publication to switch to Creative Commons licence terms, as noted at publication
References
Akerley W, Glantz M, Choy H, Rege V, Sambandam S, Joseph P, Yee L, Rodrigues B, Wingate P and Leone L (1998) Phase I trial of weekly paclitaxel in advanced lung cancer. J Clin Oncol 16: 153–158
Ardizzoni A, Hansen H, Dombernowsky P, Gamucci T, Kaplan S, Postmus P, Giaccone G, Schaefer B, Wanders J and Verweij J (1997) Phase II study of topotecan in pretreated small cell lung cancer. J Clin Oncol 15: 2090–2096
Burris HA, Awada A and Kuhn JG (1994) Phase I and pharmacokinetic studies of topotecan administered as 72 or 120 hr continuos infusion. Anticancer Drugs 5: 394–402
Chen AY and Liu LF (1994) DNA topoisomerases: essential enzymes and lethal targets. Ann Rev Pharmacol Toxicol 34: 191–218
Clark RS, Fracasso PM and Picus J (1999) A phase I study of weekly topotecan as a bolus infusion. Proc Am Soc Clin Oncol 18: 207a (abstract 793)
Dunphy F, Dunleavy T, Turcotte C, Petruska P and Pincus S (1998) Phase I study of topotecan plus carboplatin-paclitaxel in solid tumors. Proc Am Soc Clin Oncol 17: 240a (abstract 919)
Ettinger DS, Finkelstein DM and Sarma RP (1995) Phase II study of paclitaxel in patients with extensive-disease small-cell lung cancer: An Eastern Cooperative Oncology Group study. J Clin Oncol 13: 1430–1435
Fennelly D, Aghajanian C, Shapiro F, O'Flaherty C, McKenzie M, O'Connor C, Tong W, Norton L and Spriggs D (1997) Phase I and pharmacologic study of paclitaxel administered weekly in patients with relapsed ovarian cancer. J Clin Oncol 15: 187–192
Frasci G, Panza N, Comella P, Cartenì G, Guida T, Nicolella GP, Natale M, Lombardi R, Apicella A, Pacilio C, Gravina A, Lapenta L and Comella G (1999) Cisplatin-topotecan-paclitaxel weekly administration with G-CSF support for ovarian and small-cell lung cancer patients. A dose-finding study. Ann Oncol 10: 355–358
Glisson BS, Kurie JM, Perez-Soler R, Fox NJ, Murphy WK, Fossella FV, Les JS, Ross MB, Nyberg DA, Pisters KMW, Shin DM and Hong WK (1999) Cisplatin, etoposide, and paclitaxel in the treatment of patients with extensive small-cell lung carcinoma. J Clin Oncol 8: 2309–2315
Gray JR, Hainsworth JD, Burris HA, Morrissey LH, Gualtieri R, Joseph G, Steis R and Greco FA (2000) Paclitaxel, Carboplatin, and Topotecan in the treatment of Small Cell Lung Cancer: A phase II trial of the Minnie Pearl Cancer Research Network. Proc Am Soc Clin Oncol 19: 494a (abstract 1931)
Haas NB, LaCreta FP, Walczak J, Hudes GR, Brennan JM, Ozols RF and O'Dwyer PJ (1994) Phase I/pharmacokinetic study of topotecan by 24-hour continuous infusion weekly. Cancer Res 54: 1220–1226
Hainsworth JD, Gray JR, Stroup SL, Kalman LA, Patten JE, Hopkins LG, Thomas M and Greco FA (1997) Paclitaxel, carboplatin, and extended-schedule etoposide in the treatment of small-cell lung cancer: comparison of sequential phase II trials using different dose-intensities. J Clin Oncol 15: 3464–3470
Hochster H, Liebes L, Speyer J, Sorich J, Taubes B, Oratz R, Werntz J, Chachoua A, Raphael B and Vinci RZ (1994) Phase I trial of low dose continuous topotecan infusion in patients with cancer: an active and well tolerated regimen. J Clin Oncol 12: 553–559
Jacobs SA, Jett JR, Belani CP, Long JS, Day RD, Kim HD, Levitt ML and Wooley PV (1999) Topotecan and paclitaxel, an active couplet in untreated extensive disease small-cell lung cancer. Proc Am Soc Clin Oncol 18: 470a (abstract 1814)
Jett JR, Day R, Levitt M, Woolley G and Jacobs S (1997) Topotecan and paclitaxel in extensive stage small cell lung cancer patients without prior therapy. Lung Cancer 18: 13 (abstract 38)
Johnson BE, Grayson J, Makuch RW, Linnoila RI, Anderson MJ, Cohen MH, Glatstein E, Minna JD and Ihde DC (1990) Ten-year survival of patients with small-cell lung cancer treated with combination chemotherapy with or without irradiation. J Clin Oncol 8: 396–401
Kaplan ES and Meier P (1958) Non parametric estimation for incomplete observations. J Am Stat Assoc 53: 557–580
Kelly K, Wood ME and Bunn PA (1996) A phase I study of cisplatin etoposide and paclitaxel in extensive stage small-cell lung cancer. Proc Am Soc Clin Oncol 15: 400 (abstract 1214)
Kirshling LJ, Jung SH and Jett JR (1994) A phase II trial of taxol and G-CSF in previously untreated patients with extensive stage small-cell lung cancer. Proc Am Soc Clin Oncol 13: 326 (abstract 1076)
Landis SH, Murray T, Bolden S and Wingo PA (1998) Cancer statistics, 1998. CA Cancer J Clin 48: 6–29
Levitan N, McKenney J, Tahsildar H and Ettinger D (1995) Results of a phase I dose escalation trial of paclitaxel, etoposide and cisplatin followed by filgrastim in the treatment of patients with extensive stage small cell lung cancer. Proc Am Soc Clin Oncol 14: 379 (abstract 1177)
Lynch TJ, Herndon J, Lilenbaum RC, Lyss A, Miller AA and Green MG (1999) Toxicity of paclitaxel and topotecan in patients with previously untreated extensive small-cell lung cancer. Proc Am Soc Clin Oncol 18: 515a (abstract 1987)
Lynch TJ, Herndon JE, Lyss AP, Mauer A, Watson D, Miller A, Lilenbaum R and Green MR (2000) Paclitaxel + topotecan + G-CSF for previously untreated extensive Small Cell Lung Cancer: preliminary analysis of Cancer and Leukemia Group B (CALGB) 9430. Proc Am Soc Clin Oncol 19: 491a (abstract 1922)
Miller AB, Hoogstraten B, Staquet M and Winkler A (1981) Reporting results of cancer treatment. Cancer 47: 207–214
O' Reilly S, Fleming GF, Baker SD, Walczak JR, McGuire 3rd WP, Schilder RJ, Alvarez RD, Armstrong DK, Horowitz IR, Ozols RF and Rowinsky EK (1997) Phase I trial and pharmacologic trial of sequences of paclitaxel and topotecan in previously treated ovarian epithelial malignancies. J Clin Oncol 15: 177–186
Raefsky EL, Hainsworth JD, Burris HA, Hopkins LG and Greco FA (1999) Phase I trial of topotecan, paclitaxel and carboplatin in patients with advanced refractory malignancies. Cancer 85: 1179–1186
Rowinsky EK, Kaufman SH, Baker SD, Grochow LB, Chen TL, Peereboom D, Bowling MK, Sartorius SE, Ettinger DS, Forastiere AA and Donehower RC (1997) Sequences of topotecan and cisplatin phase I pharmacologic and in vitro studies to examine sequence dependence. J Clin Oncol 15: 3074–3084
Schiller JH, Kim K, Hutson P, De Vore R, Glick J, Stewart J and Johnson D (1996) Phase II study of topotecan in extensive stage Small Cell carcinoma of the lung: an Eastern Cooperative Oncology Group Trial. J Clin Oncol 14: 2345–2352
Sikov W, Akerley W, Strenger R and Cummings F (1998) Weekly high-dose paclitaxel demonstrates significant activity in advanced breast cancer. Proc Am Soc Clin Oncol 17: 112a (abstract 432)
Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10: 1–10
Slichenmyer WJ, Rowinsky EK, Donehouer RC and Kaufmann SH (1993) The current status of camptothecin analogoues as antitumor agents. J Natl Cancer Inst 85: 271–291
ten Bokkel Huinink WW, Richel DJ, Herben VMM Panday VRN, Schellens JHM, van de Vange N, Beusenberg F, Hearn S, Beijnen JH and Rodenhuis S (1998) Feasibility study of the combination of cisplatin, paclitaxel and topotecan in ovarian cancer patients. Proc Am Soc Clin Oncol 17: 351a (abstract 1353)
Tweedy CR, Andrews DF and Ball T (1999) Topotecan and paclitaxel in extensive stage small-cell lung cancer as initial therapy. Proc Am Soc Clin Oncol 18: 525a (abstract 2025)
Author information
Authors and Affiliations
Rights and permissions
From twelve months after its original publication, this work is licensed under the Creative Commons Attribution-NonCommercial-Share Alike 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
About this article
Cite this article
Frasci, G., Nicolella, G., Comella, P. et al. A weekly regimen of cisplatin, paclitaxel and topotecan with granulocyte-colony stimulating factor support for patients with extensive disease small cell lung cancer: a phase II study. Br J Cancer 84, 1166–1171 (2001). https://doi.org/10.1054/bjoc.2001.1741
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1054/bjoc.2001.1741
Keywords
This article is cited by
-
Phase I trial of weekly cisplatin, irinotecan and paclitaxel in patients with advanced gastrointestinal cancer
Investigational New Drugs (2009)
-
Phase I dose escalation study of vinorelbine and topotecan combination chemotherapy in patients with recurrent lung cancer
BMC Cancer (2007)
-
Weekly administration of topotecan–paclitaxel as second-line treatment in ovarian cancer
Cancer Chemotherapy and Pharmacology (2007)
-
Second-line chemotherapy in small cell lung cancer in a modified administration of topotecan combined with paclitaxel: a phase II study
Cancer Chemotherapy and Pharmacology (2006)