Fixed dose combination of capecitabine and cyclophosphamide in metastatic breast cancer: Results from THE ENCLOSE phase 2/3 randomized multicenter study
Sudeep Gupta,
Ghanashyam Biswas,
Suresh Babu,
Tanveer M. Maksud,
Kuntegowdennahalli C. Lakshmaiah,
Jayanti G. Patel,
Gopal Raja,
Rakesh R. Boya,
Pramod Patil,
Kakali Choudhury,
Shailesh A. Bondarde,
Rakesh S. Neve,
Guruprasad Bhat,
Gopichand Mamillapalli,
Apurva A. Patel,
Piyush Patel,
Nisarg Joshi,
Vinay Bajaj,
Mujtaba A. Khan
Affiliations
Sudeep Gupta
Tata Memorial Centre, Homi Bhabha National Institute, Mumbai, 400012, Maharashtra, India; Corresponding author. Tata Memorial Centre, 1109, HBB, Tata Memorial Hospital, Mumbai, 400012, Maharashtra, India.
Ghanashyam Biswas
Sparsh Hospital and Critical Care Pvt. Ltd., Bhubaneshwar, 751007, Odisha, India
Suresh Babu
Life Care Hospital, Bangalore, 560029, Karnataka, India
Tanveer M. Maksud
Unique Hospital - Multispeciality & Research Institute, Surat, 395002, Gujarat, India
Kuntegowdennahalli C. Lakshmaiah
Srinivasam Cancer Care Hospitals India Pvt. Ltd., Bangalore, 560076, Karnataka, India
Jayanti G. Patel
Apple Hospital, Surat, 395002, Gujarat, India
Gopal Raja
Madras Medical College and Rajiv Gandhi Govt. General Hospital, Chennai, 600003, Tamil Nadu, India
Rakesh R. Boya
Mahatma Gandhi Cancer Hospital & Research Institute, Visakhapatnam, 530017, Andhra Pradesh, India
Pramod Patil
Kailash Cancer Hospital & Research Centre, Vadodara, 391760, Gujarat, India
Kakali Choudhury
Health Point Hospital, Kolkata, 700025, West Bengal, India
Shailesh A. Bondarde
Shatabdi Superspeciality Hospital, Nashik, 422005, Maharashtra, India
Rakesh S. Neve
P.D.E.A's Ayurved Rugnalay & Sterling Multispeciality Hospital, Pune, 411044, Maharashtra, India
Guruprasad Bhat
Mallikatta Neuro Centre, Mangalore, 575003, Karnataka, India
Gopichand Mamillapalli
City Cancer Centre, Vijayawada, 520002, Andhra Pradesh, India
Apurva A. Patel
The Gujarat Cancer & Research Institute (M.P. Shah Cancer Hospital), Ahmedabad, 380016, Gujarat, India
Piyush Patel
Medical Affairs and Clinical Development, Intas Pharmaceuticals Ltd., Ahmedabad, 380054, Gujarat, India
Nisarg Joshi
Medical Affairs and Clinical Development, Intas Pharmaceuticals Ltd., Ahmedabad, 380054, Gujarat, India
Vinay Bajaj
Medical Affairs and Clinical Development, Intas Pharmaceuticals Ltd., Ahmedabad, 380054, Gujarat, India
Mujtaba A. Khan
Medical Affairs and Clinical Development, Intas Pharmaceuticals Ltd., Ahmedabad, 380054, Gujarat, India
Aim: To evaluate pharmacokinetics, efficacy and safety of fixed-dose combination (FDC) of oral capecitabine + cyclophosphamide in metastatic breast cancer (MBC) patients progressing after anthracycline and/or taxane chemotherapy. Methods: In this prospective, adaptive, phase-2/3, open-label study (CTRI/2014/12/005234), patients were randomized (1:1:1) to three FDC doses (doses/day: D1, capecitabine + cyclophosphamide 1400 mg + 60 mg; D2, 1800 mg + 80 mg; D3, 2200 mg + 100 mg) for 14 days, in 21-day cycles. In Part-I, multiple-dose pharmacokinetics and optimal dose(s) were evaluated with futility analysis. Group(s) with <3 responders based on best overall response rate (BOR, complete response [CR]+partial response [PR]), were discontinued. Efficacy (BOR, disease control rates [DCR; CR + PR + stable disease]) and safety of optimal dose(s) were evaluated in Part-II. Results: Of 66 patients (n = 22/group) in Part-I, pharmacokinetics (D1 = 7/22, D2 = 9/22, D3 = 8/22) showed dose-proportionality for cyclophosphamide and greater than dose-proportionality for capecitabine. Modified intent-to-treat (mITT) analysis showed BOR of 7.14% (1/14) in D1 (discontinued), and 22.22% (4/18) each in D2 and D3, respectively. In Part-II, 50 additional patients were randomized in D2 and D3 (n = 144; total 72 [22 + 50] patients/group). mITT analysis in D2 (n = 54) and D3 (n = 58) showed BOR of 29.63% (16/54, 95%CI: 17.45–41.81%) and 22.41% (13/58, 95%CI: 11.68–33.15%), respectively. DCR in D2 and D3 were 87.04% (47/54, 95%CI: 78.08–96.00%) and 82.76% (48/58; 95%CI: 73.04–92.48%) after 3 and 57.41% (31/54; 95%CI: 52.41–79.50%) and 50.00% (29/58; 95%CI: 40.40–67.00%), after 6-cycles, respectively. Hand-foot syndrome (16.67%), vomiting (9.72%) in D2, and hand-foot syndrome (18.06%), asthenia (15.28%) in D3 were most-common adverse events. Conclusion: FDC of capecitabine + cyclophosphamide (1800 + 80 mg/day) showed high disease control rates and good safety profile in MBC patients.
