Four cycles of TIP as second-line therapy achieved a durable CR rate in a high proportion of patients with relapsed testicular GCT. The high CR rate emphasizes the importance of patient selection according to prognostic factors to achieve a favorable outcome to conventional-dose salvage therapy.

The aim of this study was to determine the antitumor activity of 17-(Allylamino)-17-demethoxyge-ldanamycin (17-AAG), a heat shock protein 90(hsp90) inhibitor in patients with metastatic papillary renal cell carcinoma (RCC) or metastatic clear cell RCC. Eligible patients were divided into 2 cohorts based on histological subtype: papillary or clear cell RCC. All patients had advanced RCC with measurable disease, a Karnofsky performance status of at least 70, and no evidence of brain metastases. Twelve patients with clear cell RCC and 8 patients with papillary RCC were treated with 17-AAG on this phase II trial. 17-AAG was given intravenously at 220 mg/m(2) twice weekly for 2 weeks followed by a week of rest. Cycle length was 21 days. No patient in either cohort achieved a complete or partial response. Toxicities included elevated liver function tests, optic neuritis, dyspnea, fatigue, and gastrointestinal side effects. Six of the 20 patients required dose reduction. At the dose and schedule used in this trial, 17-AAG did not achieve objective response in the treatment of clear cell or papillary renal cell carcinoma patients.

The results of this trial suggest that bortezomib has an antitumor effect in individual patients with metastatic RCC. The small proportion of patients who achieved a partial response does not support routine use in metastatic RCC. Efforts to identify the molecular profile associated with clinical response or combination therapy with interferon alfa or other novel agents, may be considered.