Cisplatin-epirubicin-paclitaxel weekly administration with G-CSF support in advanced breast cancer. A Southern Italy Cooperative Oncology group (SICOG) phase II study

Purpose. It has been shown in vitro that both cisplatin and epirubicin incr ease the antitumor activity of paclitaxel. Weekly administration could give a substantial improvement in the therapeutic index of cisplatin and paclit axel. This study was aimed at defining the antitumor activity of a weekly c isplatin-epirubicin-paclitaxel (PET) administration in locally advanced or metastatic breast cancer patients. Patients and methods. Sixty-eight breast cancer patients with advanced dise ase, who had not received prior chemotherapy (except adjuvant), received we ekly cisplatin 30 mg/sqm, paclitaxel 120 mg/sqm and epirubicin 50 mg/sqm pl us G-CSF (day 3-5), for a maximum of 12 cycles. Thirty-five patients had st age IIIB and 33 stage IV disease (14 with visceral metastases). Results. All patients were evaluable for response on an intent to treat bas is. Overall, 21 complete and 38 partial responses have been recorded for an 87% ORR (95% CI = 76-94%). Fourteen CRs and 19 PRs have been registered in the 35 patients with locally advanced disease for a 94% ORR (95% CI = 81-9 9%) while 7 CRs and 19 PRs were observed in the 33 patients with metastatic disease for a 79% ORR (95% CI-61-91%). Surgery was performed in 33/35 wome n with locally advanced disease. Four of these patients (11%) showed no inv asive cancer on pathologic examination, and in an additional 8 patients tum or < 1 cm was found in the breast. Only 4/33 patients who underwent surgery relapsed. The projected one-year RFS was greater than 80%. At an 11-month median follow-up (range, 3-19), 11 patients had progressed and 5 had died a mong the 33 patients with metastatic disease, the median progression-free s urvival in this group being 14 months. Severe hematologic toxicity was unco mmon, grade 3-4 neutropenia and thrombocytopenia occurring in 32% and 4% of patients, respectively. Only 2 episodes of neutropenic sepsis were registe red. Packed red blood cell transfusions were required in 7 patients. Vomiti ng, diarrhoea, mucositis and skin toxicity were severe in 6%, 9%, 10%, and 9% of patients, respectively. Peripheral neuropathy was observed in 47% of patients. Conclusions. The weekly PET administration is a well tolerated and very eff ective approach in advanced breast cancer patients. It can produce a 40% cl inical complete response rate, with a more than 10% pCR rate in patients wi th T4 disease, and an about 80% ORR in those with distant metastases. A pha se III trial comparing PET with a standard every 3 weeks epirubicin-taxol a dministration is underway.