Taxol Combination in NCSLC

ASCO--Non-small-cell lung cancer (NSCLC) patients receiving paclitaxel(Taxol) plus cisplatin (Platinol) had longer survival and achievedhigh-er rates of response than patients receiving a current standardchemotherapy regimen of cisplatin plus etoposide (VePesid) ina multicenter phase III trial, Phillip Bonomi, MD, reported ata scientific session of the American Society of Clinical Oncology(ASCO) annual meeting in Philadelphia.

Average survival times were increased 25% to 30% in patients receivingpacli-taxel in combination with cisplatin as initial therapy inthe Eastern Cooperative Oncology Group (ECOG) trial, said Dr.Bonomi, associate professor of oncology, Rush University MedicalCenter, Chicago.

ECOG undertook the current study based on previous promising phaseII trial results in which response rates achieved with paclitaxelhovered at between 21% and 24%, and 1-year survival, at 40%, Dr.Bonomi said. It was the survival data that caught the eye of theNSCLC doctors, he said.

"The study enrollment came in like a tidal wave," Dr.Bonomi noted. "There were 600 patients accrued in 16 monthswith about 190 ultimately in each arm." Inclusion criteriaincluded histologically confirmed stage IIIb-IV NSCLC; no previouschemotherapy; adequate bone marrow, renal, and hepatic function;and no brain metastases.

Patients were randomized to one of three arms: a standard chemotherapyregimen of etoposide and cisplatin; a high 250 mg/m² doseof paclitaxel with cisplatin plus G-CSF (Neupogen); or a low 135mg/m² dose of paclitaxel with cisplatin, Dr. Bonomi said.Primary study endpoints included survival, response to therapy,and toxicity.

Compared with standard chemotherapy, paclitaxel/cisplatin extendedsurvival by 2 to 3 months, Dr. Bonomi noted. Survival averaged7.4 months for patients receiving etoposide/cisplatin, 9.6 monthsamong those receiving low-dose pacli-taxel/cisplatin, and 10.1months among those receiving high-dose paclitaxel with cisplatinplus G-CSF.

Response rates for groups receiving paclitaxel were also significantlybetter than for those on the standard etoposide/cisplatin regimen,he said. The response rate for the etoposide/cisplatin arm ofthe study was 12% while that for the low-dose paclitaxel/cisplatincombination was 26%. The high-dose paclitaxel group response ratewas 31%.

The major toxicity, which came as a surprise, Dr. Bonomi said,was neurotoxicity, experienced most frequently by high-dose paclitaxelpatients (37%), as compared with 19% for standard chemotherapyand 20% for low-dose pac-litaxel. "It is something that needsto be watched," Dr. Bonomi cautioned.

The incidence of grade IV leukopenia was relatively low, but gradeIV granulo-cytopenia rates were relatively high at 55% for thosereceiving standard chemotherapy and 65% for high-dose paclitaxel.Only three or four patients in the low-dose paclitaxel group experiencedthis problem, Dr. Bonomi said. He added: "Despite all thegranulocytopenia, the rates of infection were relatively low.The blood count goes down with paclitaxel, but it comes up quickly,and it doesn't seem that most patients get into trouble with seriousinfections."

He noted also that while thrombocyto-penia was not a serious problem,grade 3 anemia was fairly common in both of the paclitaxel arms.

David H. Johnson, MD, an ECOG investigator from Vanderbilt, commentedthat "lung cancer is extremely difficult to treat, and anysurvival advantage, even the 2 to 3 months found in this study,is meaningful to patients. Taxol is the most active agent we haveseen for NSCLC, and we are just beginning to see its full potentialin combination therapy."