MOMENTUM: A Phase I Trial Investigating 2 Schedules of Capecitabine With Aflibercept in Patients With Gastrointestinal and Breast Cancer.
BACKGROUND
Although data from preclinical and clinical studies provide a strong rationale for combining capecitabine with anti-angiogenic agents, clinical development of this fluoropyrimidine in combination with aflibercept has lagged behind other treatments. We conducted a nonrandomized, noncomparative, 2-arm, phase I trial to address this unmet need.


PATIENTS AND METHODS
Patients with chemorefractory gastrointestinal and breast cancer were sequentially recruited into a continuous (Arm A, starting dose 1100 mg/m2/day) or intermittent (Arm B, 2 weeks on/1 week off, starting dose 1700 mg/m2/day) capecitabine dosing arm. Aflibercept was administered at a flat dose of 6 mg/kg every 3 weeks in both arms. A classical 3 + 3, dose-escalation design was used. The primary objective was to establish the maximum tolerated dose, dose-limiting toxicities (DLTs), and recommended dose for phase II trials.


RESULTS
Thirty-eight eligible patients were recruited of whom 33 were assessable for DLTs (15 in arm A and 18 in arm B). Fourteen had colorectal cancer, 8 gastric cancer, and 11 breast cancer. DLTs included grade 2 hand-foot syndrome, grade 2 anorexia considered unacceptable by the patient, and grade 3 hypertension. The recommended dose for phase II trials for capecitabine was established at 1300 mg/m2/day in Arm A and 2500 mg/m2/day in Arm B with treatment-related grade ≥ 3 adverse events occurring in 47% and 50% of patients, respectively. Among 26 assessable patients, the objective response rate was 15.4% in Arm A and 7.7% in Arm B.


CONCLUSION
Combining capecitabine with aflibercept is feasible and associated with a manageable safety profile and some anti-tumor activity in patients with chemorefractory gastrointestinal and breast cancer.
['Camera|Silvia|S|', 'Deleporte|Amélie|A|', 'Bregni|Giacomo|G|', 'Trevisi|Elena|E|', 'Pretta|Andrea|A|', 'Telli|Tugba Akin|TA|', 'Polastro|Laura|L|', 'Gombos|Andrea|A|', 'Kayumba|Aline|A|', 'Ameye|Lieveke|L|', 'Piccart-Gebhart|Martine|M|', 'Awada|Ahmad|A|', 'Sclafani|Francesco|F|', 'Hendlisz|Alain|A|']
D000328:Adult D000368:Aged D000855:Anorexia D000971:Antineoplastic Combined Chemotherapy Protocols D001943:Breast Neoplasms D000069287:Capecitabine D015179:Colorectal Neoplasms D004305:Dose-Response Relationship, Drug D019008:Drug Resistance, Neoplasm D005240:Feasibility Studies D005260:Female D060831:Hand-Foot Syndrome D006801:Humans D006973:Hypertension D008297:Male D020714:Maximum Tolerated Dose D008875:Middle Aged D040262:Receptors, Vascular Endothelial Growth Factor D011993:Recombinant Fusion Proteins D066066:Response Evaluation Criteria in Solid Tumors D012720:Severity of Illness Index D013274:Stomach Neoplasms
Fluoropyrimidine Colorectal cancer gastric cancer Anti-angiogenic therapy Metronomic chemotherapy