Antonella Amodio

First-Line Treatment With Epirubicin and Vinorelbine in Metastatic Breast Cancer

PURPOSE This phase II multicenter trial was aimed at investigating the activity of epirubicin-vinorelbine combination as first-line chemotherapy in metastatic breast cancer patients. PATIENTS AND METHODS Ninety-seven patients with metastatic breast cancer and no prior exposure to anthracyclines received the following regimen: epirubicin 100 mg/m(2) by intravenous (IV) bolus infusion on day 1 plus vinorelbine 25 mg/m(2) by 30-minute IV infusion on days 1 and 5, every 3 weeks for up to eight cycles. All patients also received granulocyte colony-stimulating factor (G- CSF) on days 7 to 12 of every cycle. RESULTS Objective responses, confirmed at least 4 weeks after the first documentation, were observed in 65 out of 92 assessable patients (70.6%; 95% CI, 62% to 80%). Disease remained stable in 17 patients (18.5%). Responses were observed in all disease sites, being 94% in soft tissue, 60% in bone, and 66% in visceral disease. Median time to response, median duration of response, median time to progression, and median overall survival were 2, 9, 10, and 26 months, respectively. The dose-limiting toxicity was neutropenia, which was grade 4 in 36% of the patients, and was accompanied by fever in 26% of the cases. Grade 3 to 4 mucositis was encountered in 28% of the patients. Other toxicities were mild to moderate. No cardiotoxicity was observed. CONCLUSION The epirubicin-vinorelbine combination with G-CSF support has been shown in this study to be highly active as first-line treatment of metastatic breast cancer patients, with significant although transient toxicity. This justifies further evaluation in the neoadjuvant setting and in early-stage breast cancer.

Vinorelbine and Mitomycin C in Anthracycline-Pretreated Patients with Advanced Breast Cancer

At present, there is no satisfactory treatment for advanced breast cancer patients who have become refractory to anthracyclines. Vinca alkaloids and mitomycin C (MMC) are among the drugs most frequently used in this setting. Recently, vinorelbine (VNR) has been reported to be highly active in advanced breast cancer. Sixty advanced breast cancer patients previously treated with anthracyclines have been exposed to VNR 25 mg/m2 i.v. on days 1 and 8, and MMC 10 mg/m2 i.v. on day 1, with cycles repeated every 4 weeks. There were 3 complete and 21 partial responses for an overall response rate of 40% (CI 95%: 28-52%). Median duration of response and median survival were 7 and 10 months, respectively. Myelosuppression was the dose-limiting toxicity, but it was generally mild to moderate. Although this combination appears to be effective and well tolerated, every effort should be made to further improve treatment results in anthracycline-pretreated advanced breast cancer.

Docetaxel in Patients with Anthracycline-Resistant Advanced Breast Cancer

Objective: To better determine docetaxel activity in patients with well-defined anthracycline-resistant breast cancer. Methods: From October 1996, we carried out a phase II trial in 69 heavily pretreated patients with advanced breast cancer with docetaxel 100 mg/m2 by a 1-hour infusion on day 1, with cycles repeated every 3 weeks. Patients were classified as having primary anthracycline resistance (n = 32), secondary anthracycline resistance (n = 7), anthracycline pretreatment (n = 22) or no anthracycline pretreatment (n = 8). Results: Among 68 evaluable patients, we observed 6 (9%) complete responses and 27 (40%) partial responses, for an overall response rate of 49% (95% confidence interval 37–61%); the disease remained stable in 17 patients (25%). Responses according to the above subgroups were as follows: primary anthracycline resistance 41%, secondary anthracycline resistance 43%, anthracycline pretreatment 64% and no anthracycline pretreatment 43%. The median time to response, median time to progression and median overall survival were 2, 7 and 10 months, respectively. Myelosuppression was the dose-limiting toxicity, with grade 4 neutropenia occurring in 47% of the patients and neutropenic fever in 12%. G-CSF was added in the case of grade 4 febrile neutropenia; a 25% reduction in the dose of docetaxel was required in 4 patients. Other side effects were mild. Conclusions: The results of the present trial confirm the high activity of docetaxel in heavily pretreated patients with advanced breast cancer, including those with strictly defined anthracycline resistance.

First-Line Chemotherapy with Vinorelbine and Paclitaxel as Simultaneous Infusion in Advanced Breast Cancer

Based on preclinical data showing a synergistic activity of simultaneous administration of vinorelbine and paclitaxel, we carried out a phase II trial in previously untreated advanced breast cancer patients. Treatment consisted of vinorelbine 25 mg/m2 and paclitaxel 150 mg/m2, both drugs given by intravenous infusion over 3 h on day 1, with cycles repeated every 3 weeks. Granulocyte colony-stimulating factor, 300 μg subcutaneously, was given on days 7–12 to the first 10 patients. From October 1995 to January 1997, 43 patients with advanced breast cancer entered the study, and 41 were evaluable for response. We obtained 2 complete responses (5%) and 18 partial responses (44%), for an overall response rate of 49% (95% CI 34–64%). Median time to response, time to progression and survival were 2, 7 and 22 months, respectively. Myelosuppression was the dose-limiting toxicity, with G4 neutropenia in 21% and neutropenic fever in 7% of the patients. Other toxicities were mild. Simultaneous infusion of vinorelbine and paclitaxel is a well-tolerated and active regimen in metastatic breast cancer, with overall results similar to those reported with more toxic regimens; furthermore, it may be a good option in patients with anthracycline contraindications.

Neoadjuvant Sequential Docetaxel Followed by High-Dose Epirubicin in Combination With Cyclophosphamide Administered Concurrently With Trastuzumab. The DECT Trial.

To report the results of the DECT trial, a phase II study of locally advanced or operable HER2‐positive breast cancer (BC) treated with taxanes and concurrent anthracyclines and trastuzumab. Eligible patients (stage IIA‐IIIB HER2‐positive BC, 18–75 years, normal organ functions, ECOG ≤1, and left ventricular ejection fraction (LVEF) ≥55%) received four cycles of neoadjuvant docetaxel, 100 mg/m2 intravenously, plus trastuzumab 6 mg/kg (loading dose 8 mg/kg) every 3 weeks, followed by four 3‐weekly cycles of epirubicin 120 mg/m2 and cyclophosphamide, 600 mg/m2, plus trastuzumab. Primary objective was pathologic complete response (pCR) rate, defined as ypT0/is ypN0 at definitive surgery. We enrolled 45 consecutive patients. All but six patients (13.3%) completed chemotherapy and all underwent surgery. pCR was observed in 28 patients (62.2%) overall and in 6 (66.7%) from the inflammatory subgroup. The classification and regression tree analysis showed a 100% pCR rate in patients with BMI ≥25 and with hormone negative disease. The median follow up was 46 months (8–78). Four‐year recurrence‐free survival was 74.7% (95%CI, 58.2–91.2). Seven patients (15.6%) recurred and one died. Treatment was well tolerated, with limiting toxicity being neutropenia. No clinical cardiotoxicity was observed. Six patients (13.4%) showed a transient LVEF decrease (<10%). In one patient we observed a ≥10% asymptomatic LVEF decrease persisting after surgery. Notwithstanding their limited applicability due to the current guidelines, our findings support the efficacy of the regimen of interest in the neoadjuvant setting along with a fairly acceptable toxicity profile, including cardiotoxicity. Results on BMI may invite further assessment in future studies. J. Cell. Physiol. 231: 2541–2547, 2016.

102 P - CEF ± G-CSF As primary chemotherapy (PCT) in ≥ 3cm breast cancer (BC) patients(PTS)

Nintynine pts with ≥ 3cm BC, 56 considered having a resectable tumor (group A, T2 > 3cm or T3, N0-1, M0) and 43 a locally advanced tumor (group B, T4 and/or N2, M0), were treated with PCT consisting of 3 cycles of CEF (CTX 400 mg/m 2 , EPI 50 mg/m 2 , 5-FU 500 mg/m 2 ) iv on days 1 and 8, ± G-CSF 300 μg/day so every other day from day 5 to 17. The aims of the study were 1) to substitute conservative for mutilating surgery (group A) or to make resectable unreectable tumors (group B); 2) to improve disease free survial and overall survival (group A and B). Fiftysix pts in the group A and 41 in the group B are evaluable. There were 2 pCR and 46 pPR in group A (85.7%) and 1 pCR and 33 pPR in group B (82.9%). Only 1 pt in group A progressed during treatment. Myclosoppression was the most important side effect, with G3-G4 neutropenia in 42/58 pts (72.41%) treated with CEF plus G-CSF, and in 41/51 pts (80%) treated with CEF alone; the planned dose-intensity of CEF was maintained in 79.31% of the G-CSF pts, and in 31% of the no-G-CSF pts (p