An all-oral combination of metronomic cyclophosphamide plus capecitabine in patients with anthracycline- and taxane-pretreated metastatic breast cancer: a phase II study

• Published in: Cancer chemotherapy and pharmacology Vol. 69; no. 2; pp. 515 - 522
• Main Authors: Wang, Zhonghua, Lu, Jingsong, Leaw, Shiangjiin, Hong, Xiaonan, Wang, Jialei, Shao, Zhimin, Hu, Xichun
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.02.2012; Springer; Springer Nature B.V
• Subjects: Administration, Oral; Adult; Aged; Anorexia - chemically induced; Anthracyclines - administration & dosage; Anthracyclines - adverse effects; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - pathology; Bridged-Ring Compounds - administration & dosage; Bridged-Ring Compounds - adverse effects; Cancer Research; Capecitabine; Cyclophosphamide - administration & dosage; Cyclophosphamide - adverse effects; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fluorouracil - administration & dosage; Fluorouracil - adverse effects; Fluorouracil - analogs & derivatives; Gynecology. Andrology. Obstetrics; Hand-Foot Syndrome - etiology; Humans; Kaplan-Meier Estimate; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Metastasis; Oncology; Original Article; Pharmacology. Drug treatments; Pharmacology/Toxicology; Prospective Studies; Taxoids - administration & dosage; Taxoids - adverse effects; Treatment Outcome; Tumors; Metastatic breast cancer; Phase II; Capecitabine; Oral chemotherapy; Metronomic cyclophosphamide; Antineoplastic agent; Breast disease; Metastasis; Taxane derivatives; Phase II trial; Advanced stage; Pyrimidine nucleoside; Human; Fluoropyrimidine derivatives; Oral administration; Patient; Breast cancer; Malignant tumor; Prodrug; Mammary gland diseases; Alkylating agent; Oxazaphosphinane derivatives; Chemotherapy; Cyclophosphamide; Treatment; Nitrogen mustard; Anthracyclins; Cancer
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-011-1728-3

Purpose Oral administration of cyclophosphamide (CTX) and capecitabine may have a greater potential for treatment of metastatic breast cancer (MBC) due to anti-angiogenesis resulting from the metronomic dosage and upregulation of thymidine phosphorylase by CTX. The purpose of this phase II study was to evaluate the efficacy and safety profile of an all-oral combination of metronomic CTX plus capecitabine for women with anthracycline- and taxane-pretreated MBC. Method In this prospective single-center, open-label, phase II trial, patients with measurable disease received oral metronomic CTX 65 mg/m 2 daily on days 1–14 plus capecitabine 1,000 mg/m 2 twice daily on days 1–14. The treatment was repeated every 3 weeks, and continued until disease progression, unacceptable toxicity or withdrawal of informed consent. The primary endpoint of the study was time to progression (TTP). Results A total of 68 patients were enrolled and received 537 cycles of chemotherapy with a median of 8 cycles (range: 1–30 cycles) per patient. Sixty-six patients were evaluated for efficacy with all patients for toxicity. With a median follow-up time of 26 months, the median time to progression was 5.2 months (95% CI, 4.2–6.2 months), and the median overall survival was 16.9 months. The overall response rate was 30.3% (95% CI, 20–43%). Clinical benefit rate was 53.0% (95% CI, 38–62%). The doublet was well tolerable, with anorexia (7.5%), the only grade 3/4 adverse events occurring in more than 5% of patients. Grade 3 hand–foot syndrome was 4.4%. Conclusion The all-oral combination of metronomic CTX plus capecitabine is an effective and convenient and well-tolerated regimen for MBC. (ClinicalTrials.gov number, NCT00589901).