| General information |
| Database: | DB00930 |
| Objective: | To evaluate the in vivo effect of adding gefitinib to preoperative chemotherapy on the EGFRdependent p42/44 MAPK in operable breast cancer (BC) patients. Secondary aims: to evaluate EGFR, (p)EGFR, Ki67, apoptotic index (TUNEL test) and VEGFR2 expression from baseline to surgery, percentage of pathologic complete response (pCR), and toxicity. |
| Authors: | Guarneri V, et al |
| Title: | Phase II, randomized trial of preoperative epirubicinpaclitaxel +/ gefitinib with biomarker evaluation in operable breast cancer. |
| Journal: | Breast Cancer Res Treat. |
| Year: | 2008 |
| PMID: | 17687648 |
| Trial Design |
| Clinical Trial Id: | NA |
| Agent: | gefitinib
|
| Target: | Epidermal growth factor receptor
|
| Cancer Type: | breast cancer |
| Cancer Subtype: | breast cancer |
| Therapy Type: | com |
| Therapeutic Combination Type: | 2 |
| Therapeutic Combination Content: | epirubicinpaclitaxel + gefitinib |
| Study Type: | Phase II, randomized trial |
| Key Patients Feature: | EGFRdependent p42/44 MAPK in operable breast cancer (BC) patients |
| Biomarker: | EGFR, (p)EGFR, Ki67, apoptotic index (TUNEL test) and VEGFR2 expression |
| Biomark Analysis: | No significant differences in the expression of p42/44 MAPK, EGFR, (p)EGFR, VEGFR2, proliferation index and apoptosis were observed comparing the combined Arms A + B vs C, and comparing Arm A vs B. |
| Control Group Info: | epirubicinpaclitaxel versus epirubicinpaclitaxel + gefitinib |
| Treatment Info: | pts have been randomized to receive epirubicin 90 mg/sqm and paclitaxel 175 mg/sqm on day 1 plus: gefitinib 250 mg daily from day 5 to 16 (Arm A, intermittent), gefitinib 250 mg daily from day 1 to 21 (Arm B, continuous), or placebo (Arm C). Treatment plan: 4 courses every 3 weeks, followed by surgery. |
| Primary End Point: | efficacy; |
| Secondary End Point: | to evaluate EGFR, (p)EGFR, Ki67, apoptotic index (TUNEL test) and VEGFR2 expression from baseline to surgery, percentage of pathologic complete response (pCR), and toxicity |
| Patients Number: | 90 |
| Trial Results |
| DLT_MTD: | NA |
| Objective Response Rate: | NA |
| Disease Control Rate: | NA |
| Median Time to Progression: | NA |
| Median PFS A vs. C: | NA |
| Median OS A vs. C: | NA |
| Adverse Event(agent arm): | Overall, 10 patients discontinued the experimental treatment: 1 patient in Arm A for a grade 3 hypertransaminasemia, 4 patients in Arm B (1 treatment and cancer unrelated death; 1 grade 3 hypertransaminasemia; 1 progression of disease; 1 grade 3 skin toxicity), and 5 patients in Arm C (1 grade 2 enteritis; 1 grade 4 hypertransaminasemia; 1 perforative peritonitis; 1 severe mood alteration requiring carbamazepine; 1 major protocol deviation).Chemotherapy dose reductions or delays were necessary in 28% of courses in Arm A, 19% in Arm B and 15% in Arm C (P = ns).Grade 3-4 hematologic toxicities per treatment arms are summarized in Table 2: no significant differences were observed when comparing the two arms with chemotherapy plus gefitinib (Arms A and B) versus chemotherapy plus placebo (Arm C), nor comparing the two different schedules of gefitinib in combination with chemotherapy (Arm A vs Arm B). |
| Conclusions: | Adding gefitinib to chemotherapy did not result in different effects on the EGFRdependent pathway, proliferation, apoptosis and VEGFR2 expression as compared to placebo, while enhancing skin and mucosal toxicity. The two schedules of gefitinib (intermittent vs continuous) did not result in different biologic effects. |