Study endpoints

The primary study endpoints were OS and the time to second tumor progression (TTsP). OS was defined as the interval between randomization and death from any cause and TTsP was defined as the interval between randomization and second relapse. The secondary study endpoints were first progression-free survival (PFS, ie, the interval between randomization and first occurrence of tumor progression after first-line treatment with IP or EP), tumor response, and safety. The Response Evaluation Criteria in Solid Tumors criteria were used to evaluate the tumor response. Adverse events were evaluated using National Cancer Institute Common Toxicity Criteria-Adverse Effect version 3.0.


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Statistical analysis

The data were analyzed using the Statistical Package for the Social Sciences version 18.0 software (SPSS Inc, Chicago, IL, USA). The survival curves, PFS curves, and TTsP were evaluated by the Kaplan–Meier method, and the groups were compared using the log-rank test. P<0.05 was considered to indicate a statistically significant difference.

RESULTS

Overall survival

Median OS was 15.4 months (95% confidence interval [CI] 13.9–16.9) in group A and 15.7 months (95% CI 14.0–17.5) in group B; the difference between the two groups was not statistically significant (P=0.483, Figure 1).

Time to second tumor progression

The median TTsP was 9.5 months (95% CI 8.6–10.1) in group A and 9.9 months (95% CI 8.8–10.9) in group B. Significant difference was also observed between the two groups (P=0.361; Figure 2).

First progression-free survival

The median duration of first PFS was 6.5 months (95% CI 5.7–7.2) in group A and 6.3 months (95% CI 5.5–7.2) in group B; this difference was not statistically significant between the two groups (P=0.256; Figure 3). The median delay between first PFS and the start of second-line chemotherapy was 21 days in group A and 15 days in group B.

Objective tumor response

In first-line therapy, nine complete responses were achieved with IP (18.8%) versus eight complete responses with EP (17.8%). The disease control rates were 95.9% with IP versus 95.6% with EP (P=0.487). All patients enrolled in the study accepted second-line chemotherapy. Three complete responses were observed with EP (6.2%) and two complete responses with IP (4.4%). The disease control rates were 60% with IP and 59% with EP (P=0.514; Table 2).

(To view a larger version of Table 2, click here.)

Adverse events

There was one chemotherapy-related death in group A due to life-threatening hematological toxicity and delayed diarrhea. Grade 3/4 hematological toxicity was significantly more frequent with EP, and grade 3/4 diarrhea was significantly more frequent with IP. The frequency of adverse effects during first-line and second-line treatment in each group are summarized in Table 3. For the EP regimen, the incidence of grade 3/4 neutropenia in first-line treatment was significantly higher than that with IP, and the incidence of grade 3/4 diarrhea was significantly lower than that of IP. For the IP regimen, the incidence of grade 3/4 neutropenia was increased by second-line treatment, and diarrhea and thrombocytopenia had no difference between groups. The probability of anemia and thrombocytopenia was not statistically significant in the first-line and second-line treatment between two groups. In the two treatment groups, the patients accepted IP regimen as second-line treatment occurred 3/4 grade neutropenia was significantly higher than that of IP regimen as first-line therapy. At the same time, for the patients received the EP regimen as the first-line and second-line treatment, the incidence of grade 3/4 hematological and non-hematological toxicity changed little.

(To view a larger version of Table 3, click here.)