Sridhar Mani

Prognostic Factors for Survival in Patients with Metastatic Renal Cancer Treated with Biological Response Modifiers

PURPOSE Clinical characteristics prognostic of survival in patients with metastatic renal cell carcinoma treated with biological response modifiers are poorly understood. Understanding these prognostic features may help with better stratification of patients in clinical trials and define further appropriate treatment for each prognostic subgroup. MATERIALS AND METHODS A retrospective study of 84 patients with recurrent or metastatic renal cancer was conducted to identify prognostic factors for survival in patients who received biological response modifiers (alpha-interferon, beta-interferon, gamma-interferon and interleukin-2). RESULTS Univariate analysis identified Eastern Cooperative Oncology Group (ECOG) performance status (1 versus 0, p < 0.001), bone metastasis (p = 0.008), recent weight loss (greater than 10% of total body weight versus no loss, p = 0.028), history of nephrectomy (no versus yes, p = 0.025), recurrence at the renal bed (p = 0.043) and sarcomatoid histology (yes versus no, p < 0.001) as important prognostic indicators. Multivariate analysis of prognostic factors in this patient population indicated that ECOG performance status, sarcomatoid histology and bone metastasis were most significant, while other factors were less significant (p > 0.05) after adjusting for ECOG performance status and sarcomatoid histology. Based on the total positive number of 5 risk factors defined previously the study population separates into 3 risk groups, with a median survival from the low to high risk groups of 14.4, 10.9 and 1.3 months, respectively. Prognostic scores based only on ECOG performance status, sarcomatoid histology and bone metastasis allowed for stratification of our patients into 3 distinct groups with median survivals of 18.6, 8.4 and 3.8 months, which were also predictive of survival (p < 0.05). CONCLUSIONS Risk factors of ECOG performance status, sarcomatoid histology, bone metastasis, history of nephrectomy, recent weight loss and recurrence at the renal bed are predictive of survival in patients treated with biological response modifiers. In addition to previous findings of prognostic factors in renal cancer patients treated with chemotherapy, we identified sarcomatoid histology as an important risk factor in patients treated with biological response modifiers.

Sickle myonecrosis revisited

This review focuses on the classification of sickle myonecrosis in the context of sickle cell vaso-occlusive crisis. Further, the potential and novel use of magnetic resonance imaging to further clarify the nature of sickle crisis is discussed.

Single institution experience with recombinant gamma-interferon in the treatment of patients with metastatic renal cell carcinoma

We report the clinical course of eight patients with metastatic renal cell carcinoma (RCC) who were treated with recombinant gamma-interferon (Immuneron) as part of a phase II-III study comparing the safety and efficacy of gamma-interferon with that of medroxyprogesterone acetate (Depo-Provera). There were no objective responders among the eight patients treated with recombinant gamma-interferon at an i.v. dose of 1 mg/m(2) daily for five days every other week for four weeks then 1 mg/m(2) three times a week given every other week until there was documented disease progression or complete response (CR). Overall median survival was 17.3 months (range 1.4 to 184). The major side effects of treatment included fever/chills (75%), mild anorexia and fatigue (75%), nausea/vomiting (80%), leukopenia (38%), and abnormal liver function tests (25%). There were no life-threatening side effects observed. At our institution, in a random cohort of eight patients with metastatic RCC, recombinant gamma-interferon when given at a dose of 1 mg/m(2) per day given three times per week on an every other week schedule yields no clinical antitumor activity. A review of the literature on the use of gamma-interferon for metastatic RCC suggests that low-dose combination therapy with other cytokines may yield the best response-to-side effect ratio. Higher doses yield more responses but an added cost of more toxicity.

Case report: Pentamidine and polymorphic ventricular tachycardia revisited

Pentamidine isethionate has been associated with ventricular tachyarrhythmias, including torsade de pointes. This article reports two cases of this complication and reviews all reported cases to date. Pentamidine-induced torsade de pointes may be related to serum magnesium levels and hypomagnesemia may synergistically induce torsade. Torsade de pointes occurred after an average of 10 days of treatment with pentamidine. In these patients, no other acute side effects of pentamidine were observed. Torsade de pointes can be treated when recognized early, possibly without discontinuation of pentamidine. When QTc interval prolongation is observed, early magnesium supplementation is advocated.

Recombinant beta-interferon in the treatment of patients with metastatic renal cell carcinoma

We report on the clinical course of 15 patients with metastatic renal cell carcinoma (RCC) who were treated with recombinant beta-interferon as part of a phase I-II study. There were no objective responders among the 15 patients treated with recombinant beta-interferon at an i.v. dose escalating from 90 X 10(6) U given three times a week until there was documented disease progression or complete response (CR). Overall median survival was 24 months. One patient refused further treatment after 7 weeks. The major side effects of treatment included cardiovascular events (20%), mental status change requiring cessation of drug (6.7%), and grade 3 headaches/myalgias (26.7%). There were no life-threatening side effects observed; however, cardiac events led to the termination of treatment in three patients. Other minor toxicities included fatigue (46.7%), proteinuria (60%), diarrhea (6.7%), nausea and vomiting (13.3%), persistent fever (6.7%) and transient visual disturbance (6.7%). Thus, at our institution, in a cohort of 15 patients with metastatic RCC, recombinant beta-interferon when given i.V. at a dose < or equal to 720 X 10(6) U three times per week, yielded no clinical antitumor activity. A review of the literature on the use of beta-interferon for metastatic RCC suggests that there may be some efficacy, but our experience with escalating i.v. doses < or equal to 720 X 10(6) U given three times a week does not support it. Moreover, at these doses, one may find serious cardiovascular events although further studies need to be done in order to clearly define dose-related side effects as well as optimal efficacy-to-toxicity ratio.

Isolated Amyloidosis of the Penile Urethra and Corpus Spongiosum: A Case Report

Localized amyloidosis of the penile urethra and corpus spongiosum is rare. The pathogenesis is obscure and optimal management of such patients has not been defined. We report a case that was treated with transurethral removal of amyloid tissue, which was obstructing the urethral outlet. Previously, the patient had been treated with dilation with temporary relief of the symptoms. He was disease-free 1 1/2 years postoperatively.