CHICAGOPaclitaxel (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,
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