Paclitaxel by 24- or 1-hour infusion n combination with carboplatin in advanced non-small cell lung cancer: the Fox Chase Cancer Center experience.
A phase II trial of combination paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin included 54 chemotherapy-naive patients with advanced non-small cell lung cancer. Eligibility mandated Eastern Cooperative Oncology Group performance status of 0 or 1 and adequate hematologic, renal, and hepatic function. Paclitaxel 135 mg/m2 over 24 hours preceded carboplatin dosed to an area under the concentration-time curve of 7.5. Six planned courses were given every 3 weeks. Granulocyte colony-stimulating factor was introduced during the second and subsequent cycles, and paclitaxel increased 40 mg/m2/cycle (maximum, 215 mg/m2) in patients with absolute neutrophil and platelet nadirs exceeding 500/microL and 50,000/microL, respectively. Grade 3 or 4 neutropenia, observed in 54% of patients during cycle 1, declined to 35% during cycle 2 and to 22% or less during cycles 3 through 6. Neuropathy, myalgias/arthralgias, and thrombocytopenia were mild but cumulative. In 53 evaluable patients, the objective response rate was 62%, with 9% complete remissions and a median response duration of 6 months (range, 1 to 19+ months). At median potential follow-up of 16 months, 9% of patients remain progression free (52+ to 80+ weeks). Median survival is 12.5 months; 1-year survival is 54%. Paclitaxel/carboplatin is highly active in advanced non-small cell lung cancer; granulocyte colony-stimulating factor abrogates neutropenia as the dose-limiting toxicity, but has no effect on the cumulative incidence of thrombocytopenia or treatment delays. One-hour paclitaxel infusion is minimally myelosuppressive, logistically easier, and less costly. A follow-up study combined paclitaxel (175 mg/m2) over 1 hour followed by carboplatin (area under the concentration-time curve, 7.5). In the absence of grade 4 myelosuppression, paclitaxel was increased 35 mg/m2/cycle (maximum, 280 mg/m2). Granulocyte colony-stimulating factor was implemented only after neutropenic fever or grade 4 neutropenia. Of 17 patients entered, 13 are evaluable for toxicity and seven for response. Four patients have sustained a partial response, two a minor response, and one stable disease. The incidence of grade 3 or 4 neutropenia, thrombocytopenia, and anemia in cycle 1 was 38%, 16%, and 0%, respectively, and 72%, 28%, and 28%, respectively, during cycle 2. Major nonhematologic toxicities include myalgias and arthralgias (54%) and fatigue and neuropathy (78%), the latter cumulative and progressive over successive cycles. Preliminary data suggest comparable activity for the 1- and 24 hour paclitaxel infusions in combination with carboplatin. The more severe neuropathy of the 1-hour paclitaxel/carboplatin combination may be related to the paclitaxel dosing schema (175 mg/m2 to as high as 280 mg/m2).(ABSTRACT TRUNCATED AT 400 WORDS)
Langer
C J
CJ
Department of Medical Oncology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
Leighton
J C
JC
Comis
R L
RL
O'Dwyer
P J
PJ
McAleer
C A
CA
Bonjo
C A
CA
Engstrom
P F
PF
Litwin
S
S
Johnson
S
S
Ozols
R F
RF
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D018771:Arthralgia / Q000139:chemically induced; D016190:Carboplatin / Q000008:administration & dosage*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D018572:Disease-Free Survival; D005221:Fatigue / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D007262:Infusions, Intravenous; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000187:drug effects; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D017239:Paclitaxel / Q000008:administration & dosage*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced; D012074:Remission Induction; D015996:Survival Rate; D013921:Thrombocytopenia / Q000139:chemically induced / Q000517:prevention & control
D016179:Granulocyte Colony-Stimulating Factor; D016190:Carboplatin; D017239:Paclitaxel