Abstract 440P
Background
Approximately 50% of patients diagnosed with colorectal cancer (CRC) will develop metastatic disease (mCRC). Oxaliplatin in combination with Capecitabine prolongs survival in patients with mCRC. Chronomodulation might reduce toxicity and improve efficacy of this treatment strategy.
Methods
In this prospective phase III trial, 100 patients were randomized to receive: Arm A (XELOX30) 30 min-infusion of oxaliplatin 130 mg/m2 on day 1 plus oral Capecitabine at a total dose of 2000 mg/m2 daily with 50% of the dose in the morning and 50% of the dose in the evening; Arm B (XELOX30 Chrono) oxaliplatin: 130 mg/m2 on day 1, as a 30-min infusion between 1 and 3 p.m. Capecitabine: total daily dose of 2000 mg/m2, 20% of the dose between 7 and 9 a.m. and 80% of the dose between 6 and 8 p.m. for 14 days followed by one week rest. Six to eight cycles were recommended unless progressive disease or unacceptable toxicity occurred. Baseline radiological investigations: CT chest, PA (pelvi-abdominal) every 2 cycles for response assessment, adverse events were graded in accordance with the Common Terminology Criteria for Adverse events (v4.03, 2010).
Results
An overall objective response was observed in 48 patients (96%) for (XELOX30 Chrono) versus 42 patients (84%) (XELOX30) (P= 0.12%) with non-significant longer time to progression (PFS) for (XELOX30 Chrono) (P=1). No significant differences in the one year OS rates were observed between the two arms (87.5% versus 100%), although marginal significance was observed with P value close to significant level for (XELOX30 Chrono) (P = 0.056). Toxicity assessment showed ≥ grade II neuropathy was significantly more frequent in the XELOX30 group compared to the XELOX30 Chrono group (P= 0.003%). Subgroup analysis of the treatment arms revealed patients who died were significantly younger with more weight loss than those who survived.
Conclusions
The chronomodulated XELOX regimen may reduce overall toxicity and improve efficacy; longer follow up period may be required to confirm these results. A 30-minute infusion of oxaliplatin seems safe and did not increase the severity of peripheral neuropathy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.