Journal of Clinical Oncology, Vol 16, 153-158, Copyright © 1998 by American Society of Clinical Oncology

ARTICLES

Phase I trial of weekly paclitaxel in advanced lung cancer

W Akerley, M Glantz, H Choy, V Rege, S Sambandam, P Joseph, L Yee, B Rodrigues, P Wingate and L Leone
Rhode Island Hospital, Providence 02903, USA. wallya@brown.edu

PURPOSE: We conducted a phase I study in chemotherapy-naive patients with advanced non-small-cell lung cancer (NSCLC) to determine the maximum-tolerated dose (MTD) of paclitaxel using an extended weekly schedule. PATIENTS AND METHODS: Patients with stage IIIB/IV NSCLC were treated with paclitaxel administered weekly over 3 hours for 6 weeks of an 8-week cycle. Doses were modified for granulocyte counts less than 1,800/microL or neurotoxicity greater than grade I. Groups of three patients were entered at each dose level. The dose was escalated to the next level if less than 50% of patients developed unacceptable toxicity and received more than 80% of the intended first-cycle dose. RESULTS: Twenty-six patients were entered through six dose levels (100, 125, 135, 150, 175, and 200 mg/m2/wk). Four of six patients at the 175-mg/m2 dose level and only one of six patients at the 200-mg/m2 level received all scheduled doses of paclitaxel during cycle 1. Neutropenia was dose- limiting. Fourteen patients were treated with subsequent cycles of paclitaxel. Grade II to III neuropathy developed in five of 24 patients. It occurred more commonly with greater duration of therapy, but improved following dose reduction. Nine of 26 (35% +/- 10%) patients demonstrated an objective response. CONCLUSION: The MTD of paclitaxel using a weekly schedule is 175 mg/m2/wk for 6 of 8 weeks. Neutropenia limits dosing acutely, but neuropathy is limiting with sustained therapy. This schedule of paclitaxel results in a twofold to threefold increase in dose-intensity with less toxicity than anticipated from conventional dosing. Further evaluation of this schedule is warranted to assess efficacy and toxicity of prolonged administration.

This article has been cited by other articles:

				D. Normolle and T. Lawrence Designing Dose-Escalation Trials With Late-Onset Toxicities Using the Time-to-Event Continual Reassessment Method J. Clin. Oncol., September 20, 2006; 24(27): 4426 - 4433. [Abstract] [Full Text] [PDF]

				A. V. Boddy, E. R. Plummer, R. Todd, J. Sludden, M. Griffin, L. Robson, J. Cassidy, D. Bissett, A. Bernareggi, M. W. Verrill, et al. A Phase I and Pharmacokinetic Study of Paclitaxel Poliglumex (XYOTAX), Investigating Both 3-Weekly and 2-Weekly Schedules Clin. Cancer Res., November 1, 2005; 11(21): 7834 - 7840. [Abstract] [Full Text] [PDF]

				S. Mielke, A. Sparreboom, S. M. Steinberg, H. Gelderblom, C. Unger, D. Behringer, and K. Mross Association of Paclitaxel Pharmacokinetics with the Development of Peripheral Neuropathy in Patients with Advanced Cancer Clin. Cancer Res., July 1, 2005; 11(13): 4843 - 4850. [Abstract] [Full Text] [PDF]

				J. Kikuchi, K. Yamazaki, I. Kinoshita, H. Asahina, M. Imura, E. Kikuchi, J. Konishi, N. Shinagawa, H. Oki, H. Dosaka-Akita, et al. Phase I Trial of Carboplatin and Weekly Paclitaxel in Patients With Advanced Non-small-cell Lung Cancer Jpn. J. Clin. Oncol., September 1, 2004; 34(9): 505 - 509. [Abstract] [Full Text] [PDF]

				M. Neubauer, J. Schwartz, J. Caracandas, P. Conkling, D. Ilegbodu, T. Tuttle, and L. Asmar Results of a Phase II Study of Weekly Paclitaxel Plus Carboplatin in Patients With Extensive Small-Cell Lung Cancer With Eastern Cooperative Oncology Group Performance Status of 2, or Age >= 70 Years J. Clin. Oncol., May 15, 2004; 22(10): 1872 - 1877. [Abstract] [Full Text] [PDF]

				M. B. Polee, A. Sparreboom, F. A. L. M. Eskens, R. Hoekstra, J. van de Schaaf, J. Verweij, G. Stoter, and A. van der Gaast A Phase I and Pharmacokinetic Study of Weekly Paclitaxel and Carboplatin in Patients with Metastatic Esophageal Cancer Clin. Cancer Res., March 15, 2004; 10(6): 1928 - 1934. [Abstract] [Full Text] [PDF]

				E. Esteban, L. Gonzalez de Sande, Y. Fernandez, N. Corral, J Fra, I. Muniz, J. M. Vieitez, I. Palacio, J. L. Fernandez, E. Estrada, et al. Prospective randomised phase II study of docetaxel versus paclitaxel administered weekly in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy Ann. Onc., November 1, 2003; 14(11): 1640 - 1647. [Abstract] [Full Text] [PDF]

				C. M. F. Kruijtzer, H. Boot, J. H. Beijnen, H. L. Lochs, F. X. Parnis, A. S. T. Planting, J. M. G. Pelgrims, R. Williams, R. A. A. Mathot, H. Rosing, et al. Weekly oral paclitaxel as first-line treatment in patients with advanced gastric cancer Ann. Onc., February 1, 2003; 14(2): 197 - 204. [Abstract] [Full Text] [PDF]

				C.M.F. Kruijtzer, J.H.M. Schellens, J. Mezger, M.E. Scheulen, U. Keilholz, J.H. Beijnen, H. Rosing, R.A.A. Mathot, S. Marcus, H. van Tinteren, et al. Phase II and Pharmacologic Study of Weekly Oral Paclitaxel Plus Cyclosporine in Patients With Advanced Non-Small-Cell Lung Cancer J. Clin. Oncol., December 1, 2002; 20(23): 4508 - 4516. [Abstract] [Full Text] [PDF]

				O. Juan, A. Albert, F. Ordono, R. Casany, V. Caranana, J. M. Campos, and V. Alberola Low-dose Weekly Paclitaxel as Second-line Treatment for Advanced Non-small Cell Lung Cancer: a Phase II Study Jpn. J. Clin. Oncol., November 1, 2002; 32(11): 449 - 454. [Abstract] [Full Text] [PDF]

				H. Gelderblom, K. Mross, A. J. ten Tije, D. Behringer, S. Mielke, D. M. van Zomeren, J. Verweij, and A. Sparreboom Comparative Pharmacokinetics of Unbound Paclitaxel During 1- and 3-Hour Infusions J. Clin. Oncol., January 15, 2002; 20(2): 574 - 581. [Abstract] [Full Text] [PDF]

				O. S. Breathnach, M. S. Georgiadis, B. S. Schuler, P. Pizzella, V. Llorens, V. Kasturi, S. M. Steinberg, K. O’Neil, C. H. Takimoto, and B. E. Johnson Phase II Trial of Paclitaxel by 96-Hour Continuous Infusion in Combination with Cisplatin for Patients with Advanced Non-Small Cell Lung Cancer Clin. Cancer Res., July 1, 2000; 6(7): 2670 - 2676. [Abstract] [Full Text]

				W. Akerley III Paclitaxel in Advanced Non-Small Cell Lung Cancer : An Alternative High-Dose Weekly Schedule Chest, April 1, 2000; 117(4_suppl_1): 152S - 155S. [Abstract] [Full Text] [PDF]

				M. A. Socinski Single-Agent Paclitaxel in the Treatment of Advanced Non-Small Cell Lung Cancer Oncologist, October 1, 1999; 4(5): 408 - 416. [Abstract] [Full Text]

				G. Frasci, N. Panza, P. Comella, G. P. Nicolella, M. Natale, L. Manzione, D. Bilancia, R. Cioffi, L. Maiorino, G. De Cataldis, et al. Cisplatin, Gemcitabine, and Paclitaxel in Locally Advanced or Metastatic Non-Small-Cell Lung Cancer: A Phase I-II Study J. Clin. Oncol., August 1, 1999; 17(8): 2316 - 2316. [Abstract] [Full Text] [PDF]