Phase I/II trial of external irradiation plus medium-dose brachytherapy given concurrently to liposomal doxorubicin and cisplatin for advanced uterine cervix carcinoma

Background and Purpose: Although the standard of care for patients with Locally advanced uterine cervix carcinoma is cisplatin-(CDDP-) based chemotherapy and irradiation (RT), the optimal regimen remains to be elucidated. A phase I/II study was conducted to evaluate the dose Limiting toxicity (DLT) and the maximum tolerated dose (MTD) of liposomal doxorubicin (Caelyx) combined with CDDP and RT for cervical cancer. Patients and Methods: 24 patients with stage IIB-IVA were enrolled (Table 1). They all received external RT (up to 50.4 Gy) and two medium-dose rate (MDR) brachytherapy implants (20 Gy each at point A). The Caelyx starting dose of 7 mg/m(2)/week was increased in 5-mg/m(2) increments to two levels. The standard dose of CDDP was 20-25 mg/m(2)/week. Results: Concurrent chemoradiation (CCRT) sequelae and the DLTs (grade 3 myelotoxicity and grade 3 proctitis in five patients treated at the 17 mg/m(2)/week Caelyx dose level) are shown in Tables 2, 3, 4, and 5. After a median follow-up time of 17.2 months (range 4-36 months), four patients had died, 15 showed no evidence of progressive disease, and five (20.8%, 95% confidence interval [CI]: 12.5-29.1%) were alive with relapse (Figure 1). There were seven complete (29.1%, 95% CI: 19.8-38.4%) and 17 partial clinical responses (95% CI: 61.1-80.1%). The median progression-free survival was 10.4 months. Causes of death were local regional failure with or without paraaortic node relapse combined with distant metastases (Table 6). Conclusion: The MTD of Caelyx given concurrently with CDDP and RT was determined at the 12 mg/m(2)/week dose level. The above CCRT schema is a well-tolerated regimen, easy to administer in ambulatory patients, and results appear promising

Management of invasive bladder cancer in patients who are not candidates for or decline cystectomy

Bladder cancer is a common malignancy seen in older adults with coexisting medical illnesses. The management of patients with muscle invasive disease includes perioperative chemotherapy and radical cystectomy; however, patients may decline surgery and older patients with comorbid conditions may not be candidates for surgery and thus alternative treatment strategies are needed. Trimodality bladder preservation protocols for muscle invasive bladder cancer have generally included only those patients who are candidates for a salvage cystectomy. In this review, we discuss the current status of bladder preservation treatment options for patients with muscle-invasive disease who are not candidates for cystectomy or who decline surgery and highlight the need for clinical trials investigating novel treatment approaches in this older patient population