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

J Thorac Oncol. 2008 May;3(5):521-6. doi: 10.1097/JTO.0b013e31816de2a7.

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.

Publication types

  • Clinical Trial, Phase I
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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