In the late 1980s, Eastern Cooperative Oncology Group (ECOG) investigators
conducted a series of phase III trials to evaluate a variety of combination
chemotherapy regimens in patients with non-small-cell lung cancer (NSCLC).
The results showed that cisplatin (Platinol)-containing regimens produced
a response rate of approximately 25%, a median survival duration of six
months, and a one-year survival rate of 19%. None of the regimens was associated
with superior survival compared with any other regimen.
At about the same time, a series of single-agent phase II trials showed
that paclitaxel (Taxol) produced a 21% response rate and a 40% one-year
survival rate in patients with NSCLC. Investigators at the M. D. Anderson
Cancer Center in Houston observed similar results with paclitaxel. Based
on these observations, ECOG investigators initiated a phase III trial to
evaluate the potential impact of paclitaxel on survival in patients with
Eligibility requirements for this trial included histologic/cytologic
confirmation 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 evidence
of uncontrolled hyperglycemia; no previous chemotherapy; and written informed
Patients were randomly assigned to one of three regimens:
- The first consisted of cisplatin, 75 mg/m² intravenously (IV)
on day one, plus etoposide (VePesid), 100 mg/m² IV on days one, two,
- In the second regimen, paclitaxel, 250 mg/m² IV over 24 hours
was followed by cisplatin, 75 mg/m² on day two, plus oral granulocyte
colony-stimulating factor (G-CSF), 5 µg/kg starting on day three
and continuing until the granulocyte count was greater than 10,000/cells/mm³.
- The third consisted of paclitaxel, 135 mg/m²IV over
24 hours, followed by cisplatin, 75 mg/m² IV on day two.
Each regimen was repeated every 21 days. The major objectives of this
trial were to compare survival, response, and toxicity among the three
Between August 1993 and December 1994, 600 patients were entered into
this trial. The number of eligible patients treated with each regimen was
194 with cisplatin/etoposide, 190 with paclitaxel/cisplatin/G-CSF, and
187 with paclitaxel/cisplatin. Comparison of patient characteristics revealed
no significant differences between the treatment groups. Median age was
61 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 the
incidence of deaths that were possibly related to treatment was similar
to 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 the
paclitaxel/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/etoposide
and paclitaxel/cisplatin/G-CSF groups (P < .001) and between
the cisplatin/etoposide and paclitaxel/cisplatin groups (P < .001);
there was no significant difference in response for patients treated with
paclitaxel/cisplatin vs paclitaxel/cisplatin/G-CSF (P = .308).
Preliminary survival analysis revealed a trend toward longer survival
in patients treated with the paclitaxel regimens.
Both paclitaxel regimens were associated with significantly higher response
rates compared with etoposide/cisplatin, and preliminary survival analyses
suggest that the paclitaxel regimens may also be associated with superior