Asbestos Cancer Update 2008

Medical Oncology, Yale University School of Medicine, Section of Medical Oncology, New Haven, Connecticut, USA bOncology Unit, Third Department of Medicine, Athens Medical School, Sotiria General Hospital, Athens, Greece.

Xeloda (capecitabine), a thymidine phosphorylase activated fluoropyrimidine carbamate, is currently the only universally approved orally administered 5-fluorouracil (5-FU) prodrug. It belongs to a newer generation of orally administered fluoropyrimidines. It has been developed because of the clinical need for efficient, tolerable and convenient agents, which do not require continuous infusion. Capecitabine is not a cytotoxic drug in itself, but via a three-step enzymatic cascade, it is converted to 5-FU mainly within human cancer cells. While the drug compares favorably with 5-FU in patients with advanced or metastatic colorectal cancer and pretreated breast cancer, it also has an improved toxicity profile, mainly of gastrointestinal and dermatologic effects with a significantly lower incidence of grade 3/4 myelotoxicity compared with infusional 5-FU-based chemotherapy. Capecitabine’s selective activation within the tumor allows for less systemic toxicity events. A gradient of fluoropyrimidine toxicity is observed: high in the US and low in East Asia. In addition, there is a discrepancy in tolerance of dose among patients treated in the US vs. Europe. Although patients can take the drug orally in the convenience of their own home, the key to successful management of capecitabine is the clinician’s awareness of its severe, but low in incidence, adverse effects, and the patients’ education, emphasizing compliance with the treatment plan, prevention and timely recognition of its toxicities.

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Clinique Victor Hugo, Le Mans, France.

Objective(s): To assess efficacy and tolerability of preoperative capecitabine chemoradiation in rectal cancer. Methods: Patients received radiotherapy 45 Gy in 25 fractions over 5 weeks and capecitabine 825 mg/m(2) twice daily throughout radiotherapy. Surgery was performed 5-7 weeks after radiotherapy. The primary endpoint was pathological complete response, secondary endpoints were downstaging and tolerability. Results: Fifty-one patients were enrolled in a phase II study, median age 62 years (range 35-78). Sixty-three percent of tumours involved the lower third of the rectum, 45% were fixed. The median delivered radiotherapy dose was 44.8 Gy (range 39.6-45.0 Gy) over 33-49 days. The treatment-related grade 3 adverse events were diarrhoea (12%), skin reactions (8%) and asthenia (8%), with no grade 4 toxicity. Fifty patients underwent surgery (29 conservative) and 1 patient refused. The pathological complete response rate was 20% and a further 10% of patients had minimal residual disease. Additional tumour downstaging was seen in 28% of patients and the sphincter preservation rate was 58%. Conclusions: Preoperative capecitabine chemoradiation is well tolerated and its efficacy supports further exploration, both as a single agent and as part of new therapeutic strategies. Copyright (c) 2008 S. Karger AG, Basel.

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