Paclitaxel/Gemcitabine Active and Well Tolerated in NSCLC

CHICAGO—Paclitaxel (Taxol) and gemcitabine (Gemzar) administered on a frequent basis elicited significant first-line activity against advanced non-small-cell lung cancer (NSCLC), producing an overall response rate of 31% in 27 evaluable patients.

The regimen also was well tolerated, with grade 3 neutropenia in 28% of cycles being the most common hematologic toxicity, Heidi Gillenwater, MD, reported at the Second International Chicago Symposium on Malignancies of the Chest and Head & Neck. Dr. Gillenwater is assistant professor of internal medicine, Division of Hematology/Oncology, University of Virginia, Charlottesville.

Dr. Gillenwater and other investigators from the University of Virginia and the University of North Carolina, Chapel Hill, decided to test the paclitaxel and gemcitabine combination because each drug is cytotoxic in NSCLC, and the toxicity profiles of the drugs do not overlap.

Because the drugs have a mechanism of action that is cell-cycle and cell-phase specific, the investigators believed their efficacy might be optimized by frequent administration.

The researchers also assessed whether gemcitabine infusions at a rate of 10 mg/m²/min would achieve the most effective concentration. Dr. Gillenwater explained that, as a nucleoside analog, gemcitabine is activated intracellularly by deoxycytidine kinase. Gemcitabine concentrations between 10 and 20 µM may optimize this activation pattern.

A total of 29 patients with stage IIIB NSCLC with pleural effusion or stage IV disease who had received no previous treatment were evaluated after receiving paclitaxel 100 mg/m² infused over 3 hours followed by gemcitabine 800 mg/m² infused over 80 minutes on days 1 and 8 every 21 days.

After a median of four cycles and a total of 137 cycles, 12 patients have achieved a partial response; none demonstrated a complete response, and 17 have stable disease.

Side Effects

In addition to grade 3 neutropenia, which was observed in 28% of cycles, grade 4 neutropenia occurred in 8% of cycles, and grade 3 thrombocytopenia in 2.9% of cycles.

Among the nonhematologic toxicities were grade 3 pneumonia, which occurred in 5 cycles, pulmonary embolism in 4 cycles, dyspnea in 10 cycles, and nausea and vomiting in 1 cycle.

The goal of achieving concentrations of gemcitabine between 10 and 20 µM was met, with the majority of patients achieving a concentration of 20 µM, Dr. Gillenwater said.