Highly toxic chemo may be effective in bladder TCC

The purpose of the trial was to assess the efficacy and toxicity of the regimen known as PCaG-paclitaxel (Abraxane, Onxol, Taxol), carboplatin (Paraplatin), and gemcitabine (Gemzar)-in 68 patients with muscle-invasive bladder cancer.

Study presenter Niklas J. Mackler, MD, a hematology/oncology fellow working with lead author David Smith, MD, and colleagues at the University of Michigan, Ann Arbor, told Urology Times that earlier trials had shown that patients who received MVAC-the regimen of methotrexate (Trexall), vinblastine (Velban), doxorubicin (Adriamycin), and cisplatin (Platinol)-prior to cystectomy had a better survival rate than those who did not. The difficulty with the MVAC regimen is its toxicity, he said.

Arm II comprised 37 patients with a median age of 58 years and more advanced tumor: either invading other organs (T4) or with lymph node involvement (N1). Due to the more advanced stage of their disease, these patients are not considered resectable. The endpoint for arm II was to assess how many patients could become resectable by shrinking the tumor. In this arm, patients received up to six cycles of therapy.

Of patients in arm I, 22 (71%) were evaluable. Seven of the evaluable patients in this group (32%) achieved complete response, and an additional patient had residual noninvasive disease.

In arm II, 29 patients (78%) were evaluable for response, with 24 of the evaluable patients (83%) deemed surgically resectable. Twenty patients underwent cystectomy, among whom five had pT0 and two had residual carcinoma in situ.

Throughout the trial, a total of 252 cycles of therapy were delivered: 80 in arm I and 172 in Arm II, and 161 patients received the full dose of PCaG.

More than 75% of all patients in both groups reported grade 3 or 4 toxicities. In both groups, the most common toxicity was neutropenia. Two patients experienced grade 3 neuropathy, one patient had grade 3 myalgia, and one, grade 3 fatigue. Seven patients died of various causes, six of them in arm I and none in arm II. As a result, arm I was discontinued before patient accrual was completed, although only one death could be directly attributed to the chemotherapy.

"While most of the deaths did not appear to be directly related to the chemotherapy, their role is difficult to exclude," Dr. Mackler said. "The combination of paclitaxel, gemcitabine, and carboplatin is feasible and had complete pathologic response rates that appear to be comparable to other active regimens, such as MVAC. More studies are needed to assess the efficacy and reduce the toxicity of neoadjuvant therapy for bladder cancer."