Efficacy and Safety of the All-Oral Schedule of Metronomic Vinorelbine and Capecitabine in Locally Advanced or Metastatic Breast Cancer Patients: The Phase I-II VICTOR-1 Study

Abstract

Background. Vinorelbine (VRB) and capecitabine (CAPE) are demonstrated to be active in pretreated metastatic breast cancer patients. Different studies have demonstrated that the metronomic treatment is active with an acceptable toxicity profile. We designed a Phases I-II study to define the MTD of oral metronomic, VRB, and CAPE. Patients and Methods. Phase I: fixed dose of CAPE was 500 mg thrice a day, continuously. Level I of VRB was 20 mg/tot thrice a week for 3 weeks (1 cycle). Subsequent levels were 30 mg/tot and 40 mg/tot (Level III), respectively, if no Grades 3-4 toxicity were observed in the previous level. Phase II: further 32 patients received the MTD of VRB plus CAPE for a total of 187 cycles to confirm toxicity profile. Results. 12 patients were enrolled in Phase I and 22 in Phase II. Phase I: the MTD of VRB was 40 mg. Phase II: 187 cycles were delivered, observing 5.9% of Grades 3-4 toxicity. 31 patients are evaluable for efficacy, obtaining a clinical benefit rate of 58.1%. Conclusion. MTD of VRB with fixed dose of CAPE was 40 mg thrice a week and was the recommended dose for the ongoing Phase II multicenter study.

Metronomic chemotherapy with oral vinorelbine (mVNR) and capecitabine (mCAPE) in advanced HER2-negative breast cancer patients: is it a way to optimize disease control? Final results of the VICTOR-2 study

“…In another study [6], the combination of a low protracted dose of temozolomide, mVNR, and radiotherapy for newly diagnosed brain metastases from breast cancer resulted in CBR of 77 % and ORR of 52 %. Finally, the single-center phase I/II VICTOR-1 study [4] reported similar results to those shown by other studies with a clinical benefit rate (CBR) of 58.1 %. Taken together, these data and those from the present study suggest that mCT, when administered with highly active and synergistic drugs such as VNR and CAPE, is able to induce encouraging DCR.…”

“…Several phase II studies have investigated metronomic vinorelbine (mVNR) in the treatment of breast cancer [4–8]. mVNR demonstrated long-lasting disease control combined with a good toxicity profile.…”

“…Our group recently published the results of the VICTOR-1 study, showing that the all-oral metronomic combination of VNR and CAPE is highly active in a population of hormone receptor (HR)-positive/HER2-negative advanced breast cancer patients, with a very low incidence of Grade 3–4 toxicity [4]. …”

Metronomic chemotherapy from rationale to clinical studies: A dream or reality?

“…Of the 31 patients evaluable for efficacy 58,1% obtained a clinical benefit. With regard to the safety, two cases of grade 4 leukopenia one case of grade 3 thrombocytopenia, and one case of grade II diarrhea were observed [68]. Vinorelbine was also evaluated together with cyclophosphamide in a small phase II study conducted by Pluma Jimenez et al In this study 20 patients previously treated with anthracyclines and taxanes were evaluated.…”

Dose-Dense Chemotherapy in Metastatic Breast Cancer: Shortening the Time Interval for a Better Therapeutic Index

“…This trial showed that this metronomic combination was a well-tolerated and feasible regimen with 2 complete and 10 partial responses documented [37]. In the phase I/II VICTOR-1 study, the combination of metronomic vinorelbine thrice weekly and capecitabine 500 mg thrice daily was investigated [38]. The dosage of vinorelbine could be increased up to 40 mg thrice weekly.…”