358P - Evaluation of continuous low dose versus standard dose capecitabine monotherapy as second/third-line chemotherapy for metastatic malignancies

Background

Capecitabine (CapX) monotherapy is often employed as a second/third line regimen for various malignancies in the metastatic setting. The use of radical doses of CapX in the palliative setting entails severe toxicities which makes it incompatible with the principles of palliative care. It was a local policy to offer each patient eligible for palliative CapX monotherapy the choice of a standard dose (StD) approach (1-1.25g/m2 bid on Days 1-14 of a 21 day cycle) or a continuous low dose (CLD) approach (0.5g bid daily without a break). Patients were provided information about each regimen's toxicity and efficacy. We recognized a unique retrospective opportunity to compare StD versus CLD.

Methods

After alteast one prior line of chemotherapy, 52 & 44 patients had received CapX monotherapy with StD & CLD, respectively between march 2013 & August 2016 for metastatic malignancies of the gall bladder, pancreas and stomach. Differences in toxicities/discontinuations were assessed by the Fisher Exact Test. For each patient, the date of initiation of CapX, the date of progression and the date of death were noted. The differences in survival outcomes between the two groups was assessed by the Mann Whitney U test.

Results

The incidence of Grade>2 toxicity was significantly higher in the StD compared to the CLD group (68% vs. 3.8%; p < 0.0001). Discontinuations were significantly higher in the StD compared to the CLD group (41% vs. 3.8%; p < 0.0001). The median PFS after initiation of CapX was higher in the CLD than the StD group (123 vs 106 days; z score 2.24, p 0.0251). The median OS after initiation of CapX was higher in the CLD than the StD group (199 vs 166 days; z score 1.98, p 0.047).

Conclusions

While lower toxicities and discontinuation rates were expected in the CLD arm, it was very surprising that survival outcomes too were better in the CLD group. In addition to possible pharmacodynamic advantages of the CLD approach, the better outcomes could also be attributed to better tolerability when compared to the StD approach. Further research would be worthwhile as it could potentially help spare future patients from toxicity while improving efficacy.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Swami Rama Cancer Hospital & Research Institute.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.