Phase I trial of nanoparticle albumin-bound paclitaxel in combination with gemcitabine in patients with thoracic malignancies.

Abstract

BACKGROUND:

Nab-paclitaxel has a different toxicity profile than solvent-based paclitaxel including a lower rate of severe neutropenia. This trial was designed to determine the maximum tolerated dose and dose limiting toxicities (DLT) of nab-paclitaxel in combination with gemcitabine.

METHODS:

Patients were required to have a performance status of 0 to 1, < or = three prior cytotoxic chemotherapy regimens, and preserved renal, hepatic, and bone marrow function. Patients received gemcitabine 1000 mg/m on days 1, 8 in all cohorts, and nab-paclitaxel at doses of 260, 300, 340 mg/m every 21 days depending on the treatment cohort (1 cycle = 21 days). DLT were assessed after the first cycle, and doses were escalated in cohorts of 3 to 6 patients.

RESULTS:

Eighteen patients were consented and 15 patients are evaluable [median age 62 years (range, 35-75); median number of prior treatments 3 (range, 1-4); tumor types: non-small cell lung cancer (NSCLC) (n = 8), small cell lung cancer (SCLC) (n = 6), and esophageal cancer (n = 1)]. At a nab-paclitaxel dose of 300 mg/m, 1 of 6 pts experienced a DLT (omission of day 8 gemcitabine due to absolute neutrophil count < 500), and at an nab-paclitaxel dose of 340 mg/m 2 of 3 patients experienced a DLT (1 pt grade 3 rash and pruritus; 1 pt grade 3 fatigue and anorexia). Responses were observed in NSCLC and SCLC.

CONCLUSIONS:

The maximum tolerated dose of nab-paclitaxel is 300 mg/m in combination with gemcitabine 1000 mg/m on days 1, 8 every 21 days. This combination demonstrated activity in previously treated NSCLC and SCLC patients.

• Authors: Thomas E Stinchcombe, Mark A Socinski, Carrie B Lee, D Neil Hayes, Dominic T Moore, Richard M Goldberg, E Claire Dees
• Journal: Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer (J Thorac Oncol) Vol. 3 Issue 5 Pg. 521-6 (May 2008) ISSN: 1556-1380 [Electronic] United States
• PMID: 18449006 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 130-nm albumin-bound paclitaxel
• Albumins
• Deoxycytidine
• Paclitaxel
• Gemcitabine

Topics

• Adult
• Aged
• Albumins (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Carcinoma, Small Cell (drug therapy)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Esophageal Neoplasms (drug therapy)
• Female
• Humans
• Lung Neoplasms (drug therapy)
• Male
• Middle Aged
• Nanoparticles
• Paclitaxel (administration & dosage)
• Survival Rate
• Treatment Outcome
• Gemcitabine