Phase II randomized study of dose-dense docetaxel and cisplatin every 2 weeks with pegfilgrastim and darbepoetin alfa with and without the chemoprotector BNP7787 in patients with advanced non-small cell lung cancer (CALGB 30303).

Abstract

INTRODUCTION:

We investigated dose-dense docetaxel and cisplatin in patients with measurable non-small cell lung cancer in a randomized phase II study without [A] or with [B] a putative chemoprotective agent, BNP7787.

PATIENTS AND METHODS:

Chemotherapy-naive patients with stage IIIB (effusion) or IV, performance status 0 to 1, and adequate organ function were eligible. Treatment with docetaxel 75 mg/m followed by cisplatin 75 mg/m over 1 hour day 1 with darbepoetin 200 mug day 1 and pegfilgrastim 6 mg day 2 without/with BNP7787 before cisplatin was repeated every other week for up to 6 cycles. The primary end point was to differentiate between grade >/=2 neurotoxicity rates of 30% on [A] and 10% on [B]. Feasibility was prospectively defined as febrile neutropenia in <10% of patients and </=1 treatment delay per cycles 1 to 3 and 4 to 6 in <20% of patients.

RESULTS:

Of 160 patients enrolled, 5 never started therapy and 4 were ineligible. Neurotoxicity grade >/=2 occurred in 32% on [A] and 29% on [B]. The incidence of febrile neutropenia was 4% on [A] and 3% on [B]. Treatment delays occurred in 13% and 20% of patients on [A] and [B], respectively. Completion rates for 3/6 cycles were 84%/51% on [A] and 84%/53% on [B]. Objective response rates were 55% on [A] and 51% on [B]. Median progression-free/overall survival times were 5.5/10.7 on [A] and 6.5/14.1 month on [B].

CONCLUSIONS:

This dose-dense treatment regimen is active, feasible, and tolerable. Its further investigation in the curative setting in non-small cell lung cancer should be considered. BNP7787 did not result in significant protection from neurotoxicity.

• Authors: Antonius A Miller, Xiaofei F Wang, Lin Gu, Philip Hoffman, Jamil Khatri, Frank Dunphy, Martin J Edelman, Michael Bolger, Everett E Vokes, Mark R Green, Cancer and Leukemia Group B (CALGB)
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 3 Issue 10 Pg. 1159-65 (Oct 2008) ISSN: 1556-1380 [Electronic] United States
• PMID: 18827613 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)

Chemical References

• Hematinics
• Recombinant Proteins
• Taxoids
• Erythropoietin
• Granulocyte Colony-Stimulating Factor
• Docetaxel
• Darbepoetin alfa
• pegfilgrastim
• Polyethylene Glycols
• 2,2'-dithiodiethanesulfonic acid
• Mesna
• Filgrastim
• Cisplatin

Topics

• Adenocarcinoma (drug therapy, secondary)
• Adenocarcinoma, Bronchiolo-Alveolar (drug therapy, secondary)
• Adult
• Aged
• Anemia (drug therapy)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Brain Neoplasms (drug therapy, secondary)
• Carcinoma, Non-Small-Cell Lung (drug therapy, pathology)
• Carcinoma, Squamous Cell (drug therapy, secondary)
• Cisplatin (administration & dosage)
• Darbepoetin alfa
• Docetaxel
• Dose-Response Relationship, Drug
• Drug Therapy, Combination
• Erythropoietin (analogs & derivatives, therapeutic use)
• Feasibility Studies
• Female
• Filgrastim
• Granulocyte Colony-Stimulating Factor (therapeutic use)
• Hematinics (therapeutic use)
• Humans
• Lung Neoplasms (drug therapy, pathology)
• Male
• Maximum Tolerated Dose
• Mesna (analogs & derivatives, therapeutic use)
• Middle Aged
• Neoplasm Staging
• Neutropenia (drug therapy)
• Polyethylene Glycols
• Prognosis
• Recombinant Proteins
• Survival Rate
• Taxoids (administration & dosage)