Thursday 7 October 2021

 


Fixed dose combination of capecitabine and cyclophosphamide in metastatic breast cancer: Results from THE ENCLOSE phase 2/3 randomized multicenter study

 

by 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 

 

The Breast: VOLUME 60, P147-154, DECEMBER 01, 2021

 

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.