The importance of the dose of etoposide in the initial treatment of metastatic germ cell tumors and advances in management of patients that relapse.

OBJECTIVE: The primary objective was to evaluate the effect of etoposide dose in a 3-day cisplatin/etoposide/bleomycin (PEB) regimen on progression free survival (PFS) and overall survival (OS). Secondary objectives were to determine the impact of a paclitaxel-based salvage regimen on OS and to compare the risk distribution of germ cell patients seen at a tertiary care center to that quoted in the International Germ Cell Consensus Classification (IGCCC). METHODS: A retrospective chart review of all 302 metastatic germ cell patients requiring cisplatin-based chemotherapy between January 1980 and December 2004 was conducted. Data collected on initial treatment included the dose of etoposide: 500 mg/m2/cycle (E500) or 360 mg/m2/cycle (E360) and whether the salvage treatment contained paclitaxel or not. PFS and OS were calculated. Patients were risk stratified as per IGCCC variables. RESULTS: The relapse rate and overall survival for E500 was 3% and 97% respectively compared to a relapse rate and OS rate of 29% and 80% respectively for E360. The addition of paclitaxel to salvage chemotherapy regimens for patients that relapsed results were 1/5 (20%) of patients dying compared to 26/39 (67%) for those who received a non-paclitaxel based salvage regimen. Ninety percent of seminoma patients were good risk and 10% were intermediate risk. Non-seminoma (NSGCT) patients were skewed to the good-risk category: 71% good risk, 10% intermediate risk and 18% poor risk as compared to 56%, 28% and 16% respectively as reported by the IGCCC. Five-year PFS and OS were comparable to those documented by the IGCCC with the exception of the intermediate risk NSGCT patients. CONCLUSION: This review demonstrated that PEB treatment containing higher dose etoposide was superior in terms of PFS and OS. Although the sample size was small, it appeared that paclitaxel containing salvage regimens resulted in superior outcomes compared to previously used salvage regimens. Our center had a similar risk distribution of patients as that quoted by the IGCCC.

Mechanisms of endocrine dysfunction in patients with testicular cancer.

To determine mechanisms of endocrine dysfunction in patients with testicular cancer, we performed static and dynamic testing of the hypothalamic-pituitary-testicular axis and testicular exocrine function in 13 patients and 11 normal control subjects, as well as in vitro studies of tumor tissue and remaining adjacent "normal" testicular tissue in the 13 patients. In tumor tissue, we demonstrated (a) elevated concentrations of total serum estradiol and serum estradiol not bound to sex hormone-binding globulin, (b) impaired spermatogenesis and sperm motility, and (c) blocking of multiple enzymes necessary for steroidogenesis. The data were consistent with a paracrine-endocrine mechanism in which tumor-produced human chorionic gonadotropin stimulates production of estradiol by "normal" testicular tissue but not tumor tissue, and the high estradiol levels then result in impaired spermatogenesis.

Cerebrospinal fluid levels of 2'-deoxycoformycin after systemic administration in monkeys.

2'-Deoxycoformycin (DCF) is an inhibitor of the enzyme adenosine deaminase (ADA) and has shown promise as an antileukemia agent. For the assessment of the extent to which systemically administered DCF crosses into the central nervous system (CNS), rhesus monkeys were given iv boluses of DCF. Simultaneous blood and cerebrospinal fluid (CSF) samples were assayed for DCF levels at times ranging from 10 minutes to 6 hours after the drug was given. Average peak CSF drug levels of 5.5 X 10(-8) M and 3 X 10(-7) M were reached 1 1/2 - 2 hours following injections of 0.25 and 1.0 mg DCF/kg, respectively. The ratio of peak CSF to simultaneous plasma levels was 1 to 10. Data obtained from a patient who had acute lymphocytic leukemia and who was given iv DCF were comparable. Drug levels achieved within the CSF following iv administration of 0.25 mg DCF/kg are similar to those previously demonstrated to inhibit ADA. These results may be important both for understanding DCF-related CNS toxicity and for designing combination chemotherapy with DCF.

Levels of 2'-deoxycoformycin, adenosine, and deoxyadenosine in patients with acute lymphoblastic leukemia.

2'-Deoxycoformycin (dCF), a potent inhibitor of adenosine deaminase, has recently undergone Phase I clinical trials and has been found to be therapeutically active in acute lymphoblastic leukemia. In this report, levels of dCF in plasma, plasma concentrations of adenosine and deoxyadenosine, and urine levels of deoxyadenosine were measured in leukemic patients undergoing treatment with dCF during a Phase I clinical trial. dCF was administered i.v. at a dose of 0.25 to 1.0 mg/kg (7.5 to 30 mg/sq m) for 3 consecutive days. Plasma drug levels of 2 to 6 microM were observed following the third dose of dCF, and drug accumulation occurred only at the 1-mg/kg dosage. In this limited series of patients, the plasma concentrations of adenosine and deoxyadenosine and the urine concentrations of deoxyadenosine did not show an obvious correlation with dCF dose, therapeutic response, or toxicity.

Randomized, double-blind, controlled trial of mitoxantrone/prednisone and clodronate versus mitoxantrone/prednisone and placebo in patients with hormone-refractory prostate cancer and pain.

PURPOSE: To compare the incidence of palliative response in patients with hormone-resistant prostate cancer (HRPC) treated with mitoxantrone and prednisone (MP) plus clodronate with that of patients treated with MP plus placebo. MATERIALS AND METHODS: Men with HRPC, bone metastases, and bone pain were randomly assigned to receive clodronate 1,500 mg administered intravenously (IV) or placebo every 3 weeks, in combination with mitoxantrone 12 mg/m2 IV every 3 weeks and prednisone 5 mg orally bid. Patients completed the present pain intensity (PPI) index and Prostate Cancer-Specific Quality-of-Life Instrument at each treatment visit and used a diary to record analgesic use on a daily basis. The primary end point was a reduction to zero or of two points in the PPI or a decrease of 50% in analgesic intake, without increase in either. RESULTS: The study accrued 209 eligible patients over 44 months. One hundred sixty patients (77%) had mild PPI scores (1 or 2), and 49 (24%) had moderate PPI scores (3 or 4). The primary end point of palliative response was achieved in 46 (46%) of 104 patients on the clodronate arm and in 41 (39%) of 105 patients on the placebo arm (P =.54). The median duration of response, symptomatic disease progression-free survival, overall survival, and overall quality of life were similar between the arms. Subgroup analysis suggested possible benefit in patients with more severe pain. CONCLUSION: MP provides useful palliation in symptomatic men with HRPC. Clodronate does not increase the rate of palliative response or overall quality of life. Clodronate may be beneficial to patients who have moderate pain, but this requires further confirmation.

Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points.

PURPOSE: To investigate the benefit of chemotherapy in patients with symptomatic hormone-resistant prostate cancer using relevant end points of palliation in a randomized controlled trial. PATIENTS AND METHODS: We randomized 161 hormone-refractory patients with pain to receive mitoxantrone plus prednisone or prednisone alone (10 mg daily). Nonresponding patients on prednisone could receive mitoxantrone subsequently. The primary end point was a palliative response defined as a 2-point decrease in pain as assessed by a 6-point pain scale completed by patients (or complete loss of pain if initially 1 +) without an increase in analgesic medication and maintained for two consecutive evaluations at least 3 weeks apart. Secondary end points were a decrease of > or = 50% in use of analgesic medication without an increase in pain, duration of response, and survival. Health-related quality of life was evaluated with a series of linear analog self-assessment scales (LASA and the Prostate Cancer-Specific Quality-of-Life Instrument [PROSQOLI]), the core questionnaire of the European Organization for Research and Treatment of Cancer (EORTC), and a disease-specific module. RESULTS: Palliative response was observed in 23 of 80 patients (29%; 95% confidence interval, 19% to 40%) who received mitoxantrone plus prednisone, and in 10 of 81 patients (12%; 95% confidence interval, 6% to 22%) who received prednisone alone (P = .01). An additional seven patients in each group reduced analgesic medication > or = 50% without an increase in pain. The duration of palliation was longer in patients who received chemotherapy (median, 43 and 18 weeks; P < .0001, log-rank). Eleven of 50 patients randomized to prednisone treatment responded after addition of mitoxantrone. There was no difference in overall survival. Treatment was well tolerated, except for five episodes of possible cardiac toxicity in 130 patients who received mitoxantrone. Most responding patients had an improvement in quality-of-life scales and a decrease in serum prostate-specific antigen (PSA) level. CONCLUSION: Chemotherapy with mitoxantrone and prednisone provides palliation for some patients with symptomatic hormone-resistant prostate cancer.

Phase III trial of neoadjuvant chemotherapy in patients with invasive bladder cancer treated with selective bladder preservation by combined radiation therapy and chemotherapy: initial results of Radiation Therapy Oncology Group 89-03.

PURPOSE: To assess the efficacy of neoadjuvant methotrexate, cisplatin, and vinblastine (MCV) chemotherapy in patients with muscle-invading bladder cancer treated with selective bladder preservation. PATIENTS AND METHODS: One hundred twenty-three eligible patients with tumor, node, metastasis system clinical stage T2 to T4aNXMO bladder cancer were randomized to receive (arm 1, n=61 ) two cycles of MCV before 39.6-Gy pelvic irradiation with concurrent cisplatin 100 mg/m2 for two courses 3 weeks apart. Patients assigned to arm 2 (n=62) did not receive MCV before concurrent cisplatin and radiation therapy. Tumor response was scored as a clinical complete response (CR) when the cystoscopic tumor-site biopsy and urine cytology results were negative. The CR patients were treated with an additional 25.2 Gy to a total of 64.8 Gy and one additional dose of cisplatin. Those with less than a CR underwent cystectomy. The median follow-up of all patients who survived is 60 months. RESULTS: Seventy-four percent of the patients completed the protocol with, at most, minor deviations; 67% on arm 1 and 81% on arm 2. The actuarial 5-year overall survival rate was 49%; 48% in arm 1 and 49% in arm 2. Thirty-five percent of the patients had evidence of distant metastases at 5 years; 33% in arm 1 and 39% in arm 2. The 5-year survival rate with a functioning bladder was 38%, 36% in arm 1 and 40% in arm 2. None of these differences are statistically significant. CONCLUSION: Two cycles of MCV neoadjuvant chemotherapy were not shown to increase the rate of CR over that achieved with our standard induction therapy or to increase freedom from metastatic disease. There was no impact on 5-year overall survival.

Therapeutic options in treatment of advanced carcinoma of the prostate.

Considerable controversy continues to surround the therapy of metastatic carcinoma of the prostate. Until recently orchiectomy and diethylstilbestrol (DES) were the only treatment options available. The development of megestrol acetate is of interest because of its broad spectrum of activity and excellent patient acceptability. Interim results of a study comparing megestrol acetate 120 mg/d plus mini-dose DES 0.1 mg/d with DES 3 mg/d are reported. Megestrol acetate had minimal side effects, with 2% of patients withdrawing from the megestrol acetate arm because of toxicity, compared with 37% from the DES arm. Significant cardiovascular toxicity occurred in 33% of patients taking DES and in 7% taking megestrol acetate. Both therapies achieved permanent suppression of serum testosterone to castrate levels. Time to progression and overall survival were longer with DES treatment, 17 versus 23 months and 24 versus 44 months, respectively, but this was not significant (P = .34 and P = .16, respectively). A review of the literature on the treatment of metastatic carcinoma of the prostate is presented to determine what should be recommended as standard therapy. Total androgen blockade is analyzed critically and results of therapy are compared with other modalities. Based on efficacy, cost, toxicity, and patient acceptability, orchiectomy still should be considered standard therapy and total androgen blockade should be considered experimental.

Megestrol acetate plus minidose diethylstilbestrol in the treatment of carcinoma of the prostate.

A multicenter randomized trial comparing megestrol acetate 120 mg/d, plus diethylstilbestrol (DES) 0.1 to 3 mg/d in patients with stage D2 prostate cancer was undertaken to compare the efficacy and toxicity of these two regimens. Pretreatment characteristics, including pathologic grade, performance status, age, and disease-related symptoms were similar in the two groups. Of 81 patients who have been entered in the study, 77 are evaluable for response and toxicity at a mean follow-up of 13.3 months. Using National Prostate Cancer Project (NPCP) criteria, no difference in response rate is noted (73% v 76%) or in disease-free survival and overall survival. The ability to suppress serum testosterone to castration levels and to maintain this suppression is equivalent in both treatment groups. However, treatment-related toxicity, including edema, hypertension, and gynecomastia, occurred at a significantly greater frequency, severity, and after a shorter treatment period in the DES-treated group. No difference in major cardiovascular events was noted. Since megestrol acetate plus minidose DES is equivalent to DES in achieving treatment responses in patients with carcinoma of the prostate, it is a preferable treatment because of its improved side-effect profile.

Muscle-invasive transitional cell carcinoma of the urinary bladder: a population-based study of patterns of care and prognostic factors.

PURPOSE: Population-based cancer registries can permit the study of the survivorship of all patients with a particular diagnosis regardless of patterns of referral and practice within a specific geographic distribution. The purpose of this study is to describe the patterns of care, outcome, and prognostic factors for bladder cancer in the northern region of the province of Alberta, Canada, between 1984 and 1993. METHODS AND MATERIALS: Between 1984 and 1993, 184 patients from northern Alberta were identified from the Alberta Cancer Registry as having undergone curative treatment for biopsy-proven muscle-invasive transitional cell carcinoma of the bladder. Data were obtained, by retrospective chart review, regarding the staging, pathology, treatment, and outcome of patients treated in the northern Alberta cities of Edmonton, Grande Prairie, and Red Deer, regardless of the responsible treating institution. The prognostic significance of patient-, tumor-, and treatment-related variables were tested using univariate and multivariate analysis using the Cox proportional-hazard model. RESULTS: As the primary treatment modality, 74 patients (40%) received radical radiotherapy (RT) without surgery; surgery was used alone in 81 patients (44%), and was combined with preoperative or postoperative radiotherapy in 29 patients (16%). Seventy-three (40%) patients also received concurrent, neoadjuvant, or adjuvant chemotherapy. The Kaplan-Meier estimate of median survival was 2.2 years, and the 5-year overall survival was 30%. Univariate analysis demonstrated the prognostic significance of T classification (p < 0.001), lymph node involvement (p < 0.001), complete response to RT (p = 0.001), hydronephrosis (p = 0.017), and vascular/lymphatic involvement (p = 0.035). Multivariate analysis revealed the following to have a significant association with survival: T classification (p = 0.001), lymph node involvement (p = 0.004), complete response to RT (p = 0.054), hydronephrosis (p = 0.019), and use of chemotherapy in the treatment regimen (p = 0.025). CONCLUSION: The strongest prognostic factors in this study were tumor related, and no significant differences in survival were detected between patients treated with primary surgery vs. organ-preservation approaches. A survival advantage associated with the incorporation of chemotherapy into the management schema was detected on multivariate, but not univariate, analysis. Stratification of patients based on tumor characteristics is imperative in clinical trials for invasive bladder cancer. Novel treatment approaches are required to improve survival further in patients with apparently localized disease.

Predictive factors for outcome in treatment of metastatic nonseminomatous germ cell tumors.

In recent years less intensive chemotherapy programs for patients with metastatic nonseminomatous germ cell tumors with high likelihood of cure have been proposed, and the use of innovative more intensive treatments for patients with less favorable prognosis is being explored. The development of validated prognostic classifications has thus become important. In 77 patients with metastatic nonseminomatous germ cell tumors treated with chemotherapy, the ability of various prognostic factors to predict outcome of treatment was assessed. The multifactorial prognostic classification (Indiana classification) and a mathematical predictive formula correctly allocated patients to low- or high-risk groups in 84.4 percent and 87.0 percent of cases. The multifactorial classification system (M.D. Anderson system) correctly allocated patients in 61 percent of cases. The presence of serum beta HCG levels over 1,000 mg/mL, a pure choriocarcinoma histology and possibly an extragonadal primary origin of tumor were found to predict an adverse outcome in a small number of patients. It is concluded that use of the Indiana classification or mathematical predictive formula is an accurate means of allocating patients with metastatic germ cell tumors to high- or low-risk groups and that allocation of patients with pure choriocarcinoma histology, very high beta HCG levels, or extragonadal primary origin of tumor to the poor prognosis category will improve the accuracy of prediction in a few cases.

Clinical benefits of bicalutamide compared with flutamide in combined androgen blockade for patients with advanced prostatic carcinoma: final report of a double-blind, randomized, multicenter trial. Casodex Combination Study Group.

OBJECTIVES: To compare the efficacy and tolerability of bicalutamide and flutamide, each combined with luteinizing hormone-releasing hormone analogue (LHRH-A) therapy, in patients with metastatic (Stage D2) prostate cancer. METHODS: This was a randomized, double-blind (for antiandrogen therapy), multicenter study with a two-by-two factorial design. Eight hundred thirteen patients were allocated 1:1 to bicalutamide (50 mg once daily) and flutamide (250 mg three times daily) and 2:1 to goserelin acetate (3.6 mg every 28 days) and leuprolide acetate (7.5 mg every 28 days). RESULTS: The median times to progression and death were 97 and 180 weeks for the bicalutamide plus LHRH-A group compared with 77 and 148 weeks for the flutamide plus LHRH-A group. The hazard ratio for time to progression for bicalutamide plus LHRH-A to flutamide plus LHRH-A was 0.93 (95% confidence interval [CI] 0.79 to 1.10, P = 0.41) and that for survival time was 0.87 (95% CI 0.72 to 1.05, P = 0.15). The therapies were generally well tolerated. The most common adverse event in the two groups was hot flashes. The incidence of hematuria was significantly higher for the bicalutamide plus LHRH-A group than for the flutamide plus LHRH-A group (12% versus 6%, P = 0.007), but no patient withdrew from therapy because of hematuria. There was a significantly (26% versus 12%, P < 0.001) higher incidence of diarrhea and more withdrawals for diarrhea (25 patients versus 2) for the flutamide plus LHRH-A group relative to the bicalutamide plus LHRH-A group. CONCLUSIONS: With a median follow-up time of 160 weeks, the combination of bicalutamide plus LHRH-A was well tolerated and had equivalent time to progression and survival compared with flutamide plus LHRH-A. Treatment with bicalutamide plus LHRH-A resulted in longer median survival than treatment with flutamide plus LHRH-A.

Comparison of goserelin and leuprolide in combined androgen blockade therapy.

OBJECTIVES: To perform exploratory analyses of data from a controlled trial that assessed the efficacy and tolerability of two antiandrogens, bicalutamide and flutamide, each combined with monthly depot preparations of leuprolide or goserelin, in patients with Stage D2 prostate cancer. One analysis compared goserelin plus antiandrogen therapy with leuprolide plus antiandrogen therapy; a second analysis compared the four combined androgen blockade (CAB) regimens. METHODS: This was a randomized, multicenter trial, open-label for luteinizing hormone releasing hormone analogue (LHRH-A) therapy, double-blind for antiandrogen therapy, with a two-by-two factorial design. Eight-hundred thirteen patients were allocated in a ratio of 2:1 to goserelin therapy (3.6 mg every 28 days) or leuprolide therapy (7.5 mg every 28 days) and 1:1 to bicalutamide therapy (50 mg once a day) or flutamide therapy (250 mg three times a day). The end points of time to progression and survival were assessed with a median of 160 weeks of follow-up. RESULTS: The percentages of progression events (70.9% versus 73.3%) and deaths (54.3% versus 56.8%) were similar for goserelin plus antiandrogen and leuprolide plus antiandrogen therapies. The hazard ratios for goserelin plus antiandrogen therapy to leuprolide plus antiandrogen therapy were 0.99 (95% confidence interval [CI] 0.84 to 1.18; P = 0.92) and 0.91 (95% CI 0.75 to 1.11; P = 0.34) for time to progression and survival, respectively. Goserelin plus antiandrogen and leuprolide plus antiandrogen therapies were generally well tolerated, and the side effects associated with depot administration occurred with a low frequency in the two groups. There were no significant differences among the goserelin plus bicalutamide, goserelin plus flutamide, or leuprolide plus bicalutamide therapy groups, but leuprolide plus flutamide therapy had a significantly poorer outcome than the other three therapies. The side-effect profiles for the four CAB groups were generally similar; diarrhea was more common among patients treated with flutamide and hematuria was more common among patients treated with bicalutamide. CONCLUSIONS: Although the results of these exploratory analyses should be interpreted with caution, they indicate that goserelin plus antiandrogen and leuprolide plus antiandrogen therapies are similarly well tolerated and have equivalent time to progression and survival, and that leuprolide plus flutamide therapy appears to be the least effective of the four CAB regimens.

Total androgen ablation: Canadian experience.

A multicenter randomized, double-blind trial comparing total androgen blockade obtained by the use of castration with a pure anti-androgen (nilutamide) with simple castration was begun. One hundred and five patients received the combined treatment and 103 the orchiectomy plus placebo. Several features were used to evaluate the efficacy. Bone pain responded better to combined treatment at 6 months (P = 0.042). The number of favorable responses, as evaluated by the NPCP criteria, was 61% with simple castration and 78% with the combined treatment (P = 0.013). There was no statistically significant difference between the two groups in time to progression (logrank test P = 0.462) or survival (logrank test P = 0.137) despite an increase in median survival of 5.4 months. All other measures showed no difference between the two treatments. With total androgen blockade, 50% of the patients had disease progression at 1 year, and 45% were dead at 2 years. A review of the results of similar reported studies suggests no improvement or very modest improvement with total androgen blockade over testicular androgen ablation alone.

Total androgen blockade for metastatic cancer of the prostate.

This randomized, double-blind study comparing orchiectomy plus placebo to orchiectomy plus a nonsteroid antiandrogen (Anandron) shows that total androgen blockade for metastatic cancer of the prostate provides a significantly better early objective response when compared to castration alone. This response, however, is less apparent at 18 months. The study also suggests a longer survival for the patients with total androgen blockade.

Progression-free survival as a clinical trial endpoint in advanced renal cell carcinoma.

Traditionally, overall survival (os) has been considered the "gold standard" for evaluating new systemic oncologic therapies, because death is easy to define, is easily compared across disease sites, and is not subject to investigator bias. However, as the available options for continuing therapy increase, the use of os as a clinical trial endpoint has become problematic because of the increasing crossover and contamination of trials. As a result, the approval of promising new therapies may be delayed.Many clinicians believe that progression-free survival (pfs) is a more viable option for evaluating new therapies in metastatic and advanced renal cell carcinoma. As with all endpoints, pfs has inherent biases, and those biases must be addressed to ensure that trial results are not compromised and that they will be accepted by regulatory authorities. In this paper, we examine the issues surrounding the use of pfs as a clinical trial endpoint, and we suggest solutions to ensure that data integrity is maintained.

Malignant ascites: demographics, therapeutic efficacy and predictors of survival.

Demographics, treatment patterns, treatment efficacy and clinical predictors of survival were studied in 76 consecutive patients with malignant ascites. Sixty-four percent of patients were female, and mean age was 63 years. The most common primary malignancies were ovarian cancer, carcinoma of unknown primary, breast cancer, colorectal carcinoma and lymphoma. Ascites was present at the time of diagnosis of malignancy in 39%. Diuretics were administered in 22% of patients with a 22% response in ascites; all responding patients had hepatic metastases. Systemic anticancer therapy was administered in 38%, with a 38% objective response in ascites. Five peritoneovenous shunts were placed, with one shunt functional at 2 weeks. Paracentesis was performed in 71% of patients with complications potentially due to paracentesis occurring in 24% of these patients. Median survival was 78 days from the clinical diagnosis of ascites. Multivariate analysis revealed significantly shortened survival in patients with liver metastases and elevated serum bilirubin, while ovarian cancer was a significant independent predictor of prolonged survival.

Analysis of prognostic factors in men with metastatic prostate cancer. Uro-Oncology Group of Northern Alberta.

We determined the influence of the extent of disease on bone scan, serum testosterone, patient age, performance status, method of initial diagnosis, Gleason grade, clinical stage at diagnosis, serum acid phosphatase, serum prostate specific antigen (PSA) and primary hormonal treatment on survival. The clinical and hormonal data were obtained when the presence of metastatic disease was established and treatment was to be initiated in 162 men with metastatic prostate cancer. Mean followup was 16 months (range 1 to 105 months). A total of 70 men (43.2%) died of the metastatic disease during the evaluation period. Log rank analysis revealed that only serum testosterone (p = 0.035) and extent of disease on bone scan (p = 0.003) significantly affected over-all survival. A trend (p = 0.068) towards decreased survival was observed with increasing values of PSA. Increasing values of acid phosphatase positively correlated with extent of disease on bone scan but was not a significant independent prognostic factor. Patient age, performance status, clinical stage, method of initial diagnosis, Gleason grade and type of hormonal treatment did not significantly influence survival. Upon using multivariate Cox analysis, only extent of disease on bone scan was significantly correlated with over-all survival (p less than 0.014). PSA may also be influential but longer duration of followup will be necessary. We conclude that extent of disease on bone scan is the most important prognosticator of the analyzed factors and that serum testosterone may be of value.

Auto-immune thrombocytopenia related to interferon therapy.

A patient with renal cell carcinoma developed reversible autoimmune thrombocytopenia while receiving leukocyte interferon (IFN) and subsequently fibroblast IFN. Bone marrow biopsies and elevated platelet-associated IgG were suggestive of immune thrombocytopenia. The patient's history of exposure to IFN and exclusion of other causes are most consistent with drug-induced immune thrombocytopenia. Rechallenge with acetaminophen, the only other drug the patient was receiving concurrently, failed to induce thrombocytopenia. With IFN alpha, acute thrombocytopenia resolved within 48 h, whereas after IFN beta it was 5 wk before platelet counts returned to normal. PaIgG, however, remained elevated for up to 30 wk. Sensitive in vitro tests failed to confirm drug-dependent binding of IgG to the patient's platelets. It is suggested that this patient developed interferon-induced autoimmune thrombocytopenia.