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.
