A phase III trial conducted by Eastern Cooperative Oncology Group (ECOG) investigators assessed the possible impact of paclitaxel on survival, response, and toxicity in patients with
ABSTRACT: A phase III trial conducted by Eastern CooperativeOncology Group (ECOG) investigators assessed the possible impact of paclitaxelon survival, response, and toxicity in patients with advanced non-small-celllung cancer. Three regimens were compared: cisplatin/etoposide, paclitaxel/cisplatin/granulocytecolony-stimulating factor (G-CSF), and paclitaxel/cisplatin. Patients wererandomly assigned to the regimens, each of which was repeated every 21days over a 17-month period. Response rates were 12% in the cisplatin/etoposidegroup, 31% in the paclitaxel/cisplatin/G-CSF group, and 26% in the paclitaxel/cisplatingroup. Significant differences in response were observed between the cisplatin/etoposideand paclitaxel/cisplatin/G-CSF groups and the cisplatin/etoposide and paclitaxel/cisplatingroups; there was no significant difference between patients treated withpaclitaxel/cisplatin vs paclitaxel/cisplatin/G-CSF. Both paclitaxel regimenswere associated with significantly higher response rates compared withetoposide/cisplatin. Based on preliminary survival analyses, the investigatorsconcluded that the paclitaxel regimens may be associated with superiorsurvival. [ONCOLOGY 11(Suppl):9-10, 1997]
In the late 1980s, Eastern Cooperative Oncology Group (ECOG) investigatorsconducted a series of phase III trials to evaluate a variety of combinationchemotherapy regimens in patients with non-small-cell lung cancer (NSCLC).The results showed that cisplatin (Platinol)-containing regimens produceda response rate of approximately 25%, a median survival duration of sixmonths, and a one-year survival rate of 19%. None of the regimens was associatedwith superior survival compared with any other regimen.
At about the same time, a series of single-agent phase II trials showedthat paclitaxel (Taxol) produced a 21% response rate and a 40% one-yearsurvival rate in patients with NSCLC. Investigators at the M. D. AndersonCancer Center in Houston observed similar results with paclitaxel. Basedon these observations, ECOG investigators initiated a phase III trial toevaluate the potential impact of paclitaxel on survival in patients withadvanced NSCLC.
Eligibility requirements for this trial included histologic/cytologicconfirmation of NSCLC: stage IIIB/IV disease without brain metastasis;ECOG performance status of 1 or less; measurable or evaluable disease;adequate bone marrow, renal, hepatic, and cardiac function; no evidenceof uncontrolled hyperglycemia; no previous chemotherapy; and written informedconsent.
Patients were randomly assigned to one of three regimens:
Each regimen was repeated every 21 days. The major objectives of thistrial were to compare survival, response, and toxicity among the threeregimens.
Between August 1993 and December 1994, 600 patients were entered intothis trial. The number of eligible patients treated with each regimen was194 with cisplatin/etoposide, 190 with paclitaxel/cisplatin/G-CSF, and187 with paclitaxel/cisplatin. Comparison of patient characteristics revealedno significant differences between the treatment groups. Median age was61 years. Slightly more than one-third were women, one-third were asymptomatic,and 25% had not lost more than 5% of their usual body weight. In addition,19% had stage IIIB disease, and 81% had stage IV NSCLC.
Grade 4 granulocytopenia occurred in the majority of patients, but theincidence of deaths that were possibly related to treatment was similarto results from previous ECOG NSCLC trials: 2% for cisplatin/etoposide,4.4% paclitaxel/cisplatin, and 5.3% for paclitaxel/cisplatin/G-CSF.
Response rates were 12% in the cisplatin/etoposide group, 31% in thepaclitaxel/cisplatin/G-CSF group, and 26% in the paclitaxel/cisplatin group.Comparison of responses using Fisher's exact test revealed significant differences between the cisplatin/etoposideand paclitaxel/cisplatin/G-CSF groups (P < .001) and betweenthe cisplatin/etoposide and paclitaxel/cisplatin groups (P < .001);there was no significant difference in response for patients treated withpaclitaxel/cisplatin vs paclitaxel/cisplatin/G-CSF (P = .308).
Preliminary survival analysis revealed a trend toward longer survivalin patients treated with the paclitaxel regimens.
Both paclitaxel regimens were associated with significantly higher responserates compared with etoposide/cisplatin, and preliminary survival analysessuggest that the paclitaxel regimens may also be associated with superiorsurvival.