Phase I trial of nanoparticle albumin-bound paclitaxel in combination with gemcitabine in patients with thoracic malignancies.
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.
Stinchcombe
Thomas E
TE
Multidisciplinary Thoracic Oncology Program, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-7305, USA. Thomas_Stinchcombe@med.unc.edu
Socinski
Mark A
MA
Lee
Carrie B
CB
Hayes
D Neil
DN
Moore
Dominic T
DT
Goldberg
Richard M
RM
Dees
E Claire
EC
D000328:Adult; D000368:Aged; D000418:Albumins / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018288:Carcinoma, Small Cell / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D053758:Nanoparticles; D017239:Paclitaxel / Q000008:administration & dosage; D015996:Survival Rate; D016896:Treatment Outcome; D000093542:Gemcitabine
C520255:130-nm albumin-bound paclitaxel; D000418:Albumins; D003841:Deoxycytidine; D017239:Paclitaxel; D000093542:Gemcitabine