Capecitabine/RT Can Replace Cisplatin in Elderly Bladder Cancer Patients

DETROIT-Capecitabine (Xeloda) can be safely delivered with radiation in elderly patients with urothelial cancers, and it provides effective palliation in localized and locally advanced urothelial cancers, according to Bhaumik Patel, MD (abstract 8165). "This offers a reasonable alternative in patients who are elderly or have significant comorbidities," said Dr. Patel, a Hematology/Oncology Fellow at Wayne State University, reporting on a study by Ulka Vaishampayan, MD, and colleagues. Concurrent cisplatin(Drug information on cisplatin) (Platinol) and external-beam radiation (RT) are commonly used for patients with localized or locally advanced urothelial cancer who are not candidates for surgery, but elderly patients often cannot tolerate full-dose cisplatin. Capecitabine(Drug information on capecitabine), is synergistic with RT in preclinical studies. "The 5-year survival rates for radical cystectomy or concurrent cisplatin and radiation for invasive transitional- cell urothelial cancer are 40% to 50% and 50% to 60%, respectively. Cisplatin is poorly tolerated and frequently cannot be used in the elderly population due to a higher rate of renal, neurologic, cardiac, and gastrointestinal toxicities," Dr. Patel said. "Based on the compelling preclinical synergy, ease of administration, and good tolerability data from our institution, we used concurrent capecitabine and radiation in patients with urothelial carcinoma who were not candidates for cystectomy or cisplatin- based therapy." Retrospective Review Dr. Patel reported data from a retrospective review of 14 patients who could not have cisplatin owing to poor performance status or comorbid conditions. The median age was 80 years (range, 46-88 years), and 13 patients were older than 65 years. All had highgrade transitional-cell cancers. Patients were treated with capecitabine on the days of radiation (Monday through Friday) in daily doses of 1,200- 1,800 mg/m²/day PO in two divided doses. Concurrent RT (40-45 Gy) was given using a four-field technique, to deliver the dose to a small pelvic field with a boost to a total of 54-67 Gy, in daily fractions of 1.8-2.0 Gy. Seven of 14 patients required dose modification because of toxicity, but only three required treatment interruptions. Grade 3 toxicities were seen in 9 of 14 patients, including diarrhea in 4, non-neutropenic infection in 1 patient, and dehydration in 4 patients. No severe myelosuppression or handfoot syndrome was seen. One patient did not finish planned radiation, and one has yet to finish treatments. These two patients were not evaluable for response. Two patients did not receive the boost, owing to grade 3 diarrhea in one patient and progressive disease in the other. Strong Responses Clinical complete response was seen in 10 of 12 (83%) evaluable patients who finished prescribed RT. "There were 10 complete responses and 1 partial response-a very good partial response...with complete resolution of the pelvic mass and partial response in the inguinal lymph node," Dr. Patel said. At a median follow-up duration of 10.5 months in evaluable patients, only one patient has relapsed, with distal metastases in the liver. No patients have shown any superficial or invasive local recurrence. Four patients have died: two from progressive disease, and two from exacerbation of pulmonary fibrosis. "The response rate is comparable to that seen in younger patients treated with cisplatin," Dr. Patel told ONI. "Older patients can get through the capecitabine regimen." The researchers concluded that concurrent capecitabine and RT is well tolerated, achieves effective palliation in localized and locally advanced urothelial cancer, offers an alternative to cisplatin, and should be investigated further in prospective trials.