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Susan Halabi

Publications and source records attributed to Susan Halabi.

36 records · Page 2Linked to original sources
PubMed2004

Antiandrogen withdrawal alone or in combination with ketoconazole in androgen-independent prostate cancer patients: a phase III trial (CALGB 9583).

PURPOSE: Antiandrogen withdrawal (AAWD) results in a prostate-specific antigen (PSA) response (decline in PSA level of > or =50%) in 15% to 30% of androgen-independent prostate cancer (AiPCa) patients. Thereafter, adrenal androgen ablation with agents such as ketoconazole (K) is commonly utilized. The therapeutic effect of AAWD alone was compared with simultaneous AAWD and K therapy. PATIENTS AND METHODS: AiPCa patients were randomized to undergo AAWD alone (n=132), or together with K (400 mg orally [p.o.] tid) and hydrocortisone (30 mg p.o. each morning, 10 mg p.o. each evening; n=128). Patients who developed progressive disease after AAWD alone were eligible for deferred treatment with K. RESULTS: Eleven percent of patients undergoing AAWD alone had a PSA response, compared to 27% of patients who underwent AAWD and simultaneous K (P=.0002). Objective responses were observed in 2% of patients treated with AAWD alone compared to 20% in patients treated with AAWD/K (P=.02). There was no difference in survival. PSA and objective responses were observed in 32% and 7%, respectively, of patients receiving deferred K, and were more common in patients with prior AAWD response. Treatment with K was well tolerated, and resulted in a decline in adrenal androgen levels, which rose at the time of disease progression. CONCLUSION: K has modest activity in AiPCa patients, while AAWD alone has minimal activity. Adrenal androgen levels fall with treatment with K and then climb at the time of progression, suggesting that progressive disease while on K may be due to tachyphylaxis to the adrenolytic properties of K.

Adenocarcinoma↗
PubMed2004

Eligibility and outcomes reporting guidelines for clinical trials for patients in the state of a rising prostate-specific antigen: recommendations from the Prostate-Specific Antigen Working Group.

PURPOSE: To define methodology to show clinical benefit for patients in the state of a rising prostate-specific antigen (PSA). RESULTS HYPOTHESIS: A clinical states framework was used to address the hypothesis that definitive phase III trials could not be conducted in this patient population. PATIENT POPULATION: The Group focused on men with systemic (nonlocalized) recurrence and a defined risk of developing clinically detectable metastases. Models to define systemic versus local recurrence, and risk of metastatic progression were discussed. INTERVENTION: Therapies that have shown favorable effects in more advanced clinical states; meaningful biologic surrogates of activity linked with efficacy in other tumor types; and/or effects on a target or pathway known to contribute to prostate cancer progression in this state can be considered for evaluation. OUTCOMES: An intervention-specific posttherapy PSA-based outcome definition that would justify further testing should be described at the outset. Reporting: Trial reports should include a table showing the number of patients who achieve a specific PSA-based outcome, the number who remain enrolled onto the trial, and the number who came off study at different time points. The term PSA response should be abandoned. TRIAL DESIGN: The phases of drug development for this state are optimizing dose and schedule, demonstration of a treatment effect, and clinical benefit. To move a drug forward should require a high bar that includes no rise in PSA in a defined proportion of patients for a specified period of time at a minimum. Agents that do not produce this effect can only be tested in combination. The preferred end point of clinical benefit is prostate cancer-specific survival; the time to development of metastatic disease is an alternative. CONCLUSION: Methodology to show that an intervention alters the natural history of prostate cancer is described. At each stage of development, only agents with sufficient activity should be moved forward.

Clinical Trials as Topic↗
PubMed2004

Impact of race on survival in men with metastatic hormone-refractory prostate cancer.

OBJECTIVES: To determine whether blacks with hormone-refractory prostate cancer have shorter survival compared with whites with the same disease. METHODS: Data from eight multicenter trials (four Phase II and four randomized Phase III studies) conducted by the Cancer and Leukemia Group B were combined. Eligible patients had progressive prostate cancer after androgen deprivation therapy (with documented castration levels of testosterone), an Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate hematologic, renal, and hepatic function. The proportional hazards model was used to assess the prognostic importance of race, adjusting for important factors. All statistical tests were two-sided. RESULTS: Of the 1183 patients, 15% were blacks, 45% of patients had a Gleason sum of 8 or greater, and the median age was 71 years. Of the 1183 patients, 35% had measurable disease and 89% had an Eastern Cooperative Oncology Group performance status of 0 to 1. Blacks were younger, had a shorter interval between diagnosis and study entry, and had greater prostate-specific antigen levels, lower hemoglobin levels, and a lower likelihood of prior prostatectomy than whites. The median survival was 15 months (95% confidence interval 12 to 18) for blacks compared with 14 months (95% confidence interval 13 to 15) for whites. In a multivariate analysis, adjusting for age, performance status, presence of visceral disease, hemoglobin, Gleason sum, prostate-specific antigen level, alkaline phosphatase, lactate dehydrogenase, and years since diagnosis, the hazard ratio was 0.85 (95% confidence interval 0.71 to 1.02, P = 0.08) for blacks compared with whites. CONCLUSIONS: No statistically significant difference was found in overall survival between blacks and whites with metastatic hormone-refractory prostate cancer.

Adenocarcinoma↗
PubMed2004

Progesterone receptor promoter +331A polymorphism is associated with a reduced risk of endometrioid and clear cell ovarian cancers.

OBJECTIVE: The progestagenic milieu of pregnancy and oral contraceptive use is protective against epithelial ovarian cancer. A functional single nucleotide polymorphism in the promoter of the progesterone receptor (+331A) alters the relative abundance of the A and B isoforms and has been associated with an increased risk of endometrial and breast cancer. In this study, we sought to determine whether this polymorphism affects ovarian cancer risk. METHODS: The +331G/A polymorphism was genotyped in a population-based, case-control study from North Carolina that included 942 Caucasian subjects (438 cases, 504 controls) and in a confirmatory group from Australia (535 cases, 298 controls). Logistic regression analysis was used to calculate age-adjusted odds ratios (OR). RESULTS: There was a suggestion of a protective effect of the +331A allele (AA or GA) against ovarian cancer in the North Carolina study [OR, 0.72; 95% confidence interval (95% CI), 0.47-1.10]. Examination of genotype frequencies by histologic type revealed that this was due to a decreased risk of endometrioid and clear cell cancers (OR, 0.30; 95% CI, 0.09-0.97). Similarly, in the Australian study, there was a nonsignificant decrease in the risk of ovarian cancer among those with the +331A allele (OR, 0.83; 95% CI, 0.51-1.35) that was strongest in the endometrioid/clear cell group (OR, 0.60; 95% CI, 0.24-1.44). In the combined U.S.-Australian data that included 174 endometrioid/clear cell cases (166 invasive, 8 borderline), the +331A allele was significantly associated with protection against this subset of ovarian cancers (OR, 0.46; 95% CI, 0.23-0.92). Preliminary evidence of a protective effect of the +331A allele against endometriosis was also noted in control subjects (OR, 0.19; 95% CI, 0.03-1.38). CONCLUSIONS: These findings suggest that the +331G/A progesterone receptor promoter polymorphism may modify the molecular epidemiologic pathway that encompasses both the development of endometriosis and its subsequent transformation into endometrioid/clear cell ovarian cancer.

Adenocarcinoma, Clear Cell↗
PubMed2003

A phase II study of estramustine, docetaxel, and carboplatin with granulocyte-colony-stimulating factor support in patients with hormone-refractory prostate carcinoma: Cancer and Leukemia Group B 99813.

BACKGROUND: The authors determined the safety and efficacy of estramustine, docetaxel, and carboplatin with granulocyte-colony-stimulating factor (G-CSF) support in patients with hormone-refractory prostate carcinoma. METHODS: In the current multicenter, cooperative group study, patients with advanced prostate carcinoma whose disease progressed despite androgen deprivation therapy were treated with a combination of oral estramustine(240 mg three times per day for 5 days), 70 mg/m2 of docetaxel, and carboplatin at a dose of (area under the curve) 5. G-CSF was used to minimize the neutropenia associated with this regimen. Each cycle was repeated every 21 days. RESULTS: Forty patients were treated with a median of 7 cycles of therapy. Of the 34 evaluable patients with elevated pretreatment prostate-specific antigen (PSA) levels, 23 (68%) had a > or = 50% decline in PSA and 20 (59%) had a > or = 75% decline. Twenty-one patients had measurable disease, with 1 complete response (5%) and 10 partial responses (47%), for an overall measurable response rate of 52% (95% confidence interval [95% CI], 30-74%). The most common Grade 3 or Grade 4 toxicities (according to the National Cancer Institute Common Toxicity Criteria) included neutropenia in 23% of patients, thrombocytopenia in 13%, and fatigue in 13%. Febrile neutropenia occurred in 1 patient (3%). The overall median time to disease progression was 8.1 months (95% CI, 6-10 months) and the overall survival period was 19 months (95% CI, 13-26 months). CONCLUSIONS: The combination of estramustine, docetaxel, and carboplatin with G-CSF support was found to have significant clinical activity with an acceptable toxicity profile in patients with progressive hormone-refractory prostate carcinoma.

Aged↗
PubMed2003

Androgen receptor mutations in androgen-independent prostate cancer: Cancer and Leukemia Group B Study 9663.

PURPOSE: The mechanisms responsible for prostate cancer androgen independence are diverse. Mutations of the androgen receptor (AR) gene that broaden ligand specificity have been implicated. Bone marrow specimens containing prostate tumor were obtained from men undergoing antiandrogen withdrawal for AR sequence analysis and clinical correlation. MATERIALS AND METHODS: Eligible men enrolled on a trial of antiandrogen withdrawal had a minimum prostate-specific antigen (PSA) level of 5 ng/dL that was increasing on castration therapy including an antiandrogen. With informed consent, marrow biopsies were obtained to collect prostate tumor. Additional samples were obtained from men enrolled on chemotherapy trials. AR cDNA or DNA was polymerase chain reaction-amplified, cloned, and sequenced. The AR CAG repeat length was recorded. RESULTS: One hundred eighty-four bone marrow biopsies were obtained, and 48 had prostate tumor detected by light microscopy. The ARs from these 48 samples were sequenced. Overall, five (10%) of 48 tumors had mutated ARs. AR point mutations were detected in the hormone-binding domain involved in transcription factor binding. Three mutations were novel in prostate cancer. One tumor sample had a CAG repeat length of 21, compared with germline length of 22 repeats. There was no association between detectability of AR mutations and antiandrogen withdrawal response or survival. CONCLUSION: These data suggest that AR mutations are present in approximately 10% of patients with prostate cancer who experience treatment failure with hormone therapy that included an antiandrogen. Mutations in the AR likely confer a growth advantage for a subset of progressive prostate cancers. Correlation of AR mutation with antiandrogen withdrawal response or survival could not be made.

Adenocarcinoma↗
PubMed2003

Overview of bladder cancer trials in the Cancer and Leukemia Group B.

The Cancer and Leukemia Group B (CALGB) Genitourinary Committee has developed a broad range of clinical trials across most stages of bladder cancer. Recurrence rates of superficial bladder cancer after transurethral resection range from 50-70%. Although adjuvant bacillus Calmette-Guerin reduces the risk of disease recurrence or progression, only 30% of patients have long-term disease-free survival. Because the development of novel secondline agents is needed, the CALGB is evaluating the utility of intravesicle gemcitabine as well as an oral proapoptotic agent (CP-461). In patients with locally advanced disease with an increased risk of disease recurrence after cystectomy, a randomized trial of conventional chemotherapy versus sequential dose-dense therapy is under development. The gemcitabine/cisplatin combination has become a commonly used regimen for the treatment of advanced transitional cell carcinoma (TCC). The CALGB is undertaking a Phase II study that incorporates a fixed dose rate gemcitabine infusion in this regimen, together with a selective epidermal growth factor receptor tyrosine kinase inhibitor, Iressa (Astra Zeneca, Wilmington, DE). In patients with renal insufficiency, a regimen of carboplatin, gemcitabine, and Iressa is planned. Novel agents, including arsenic trioxide and trastuzumab (Herceptin; Genentech, Inc., South San Francisco, CA), are being evaluated as secondline therapy in patients with advanced TCC who have disease progression after frontline therapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2003

Prognostic model for predicting survival in men with hormone-refractory metastatic prostate cancer.

PURPOSE: To develop and validate a model that can be used to predict the overall survival probability among metastatic hormone-refractory prostate cancer patients (HRPC). PATIENTS AND METHODS: Data from six Cancer and Leukemia Group B protocols that enrolled 1,101 patients with metastatic hormone-refractory adenocarcinoma of the prostate during the study period from 1991 to 2001 were pooled. The proportional hazards model was used to develop a multivariable model on the basis of pretreatment factors and to construct a prognostic model. The area under the receiver operating characteristic curve (ROC) was calculated as a measure of predictive discrimination. Calibration of the model predictions was assessed by comparing the predicted probability with the actual survival probability. An independent data set was used to validate the fitted model. RESULTS: The final model included the following factors: lactate dehydrogenase, prostate-specific antigen, alkaline phosphatase, Gleason sum, Eastern Cooperative Oncology Group performance status, hemoglobin, and the presence of visceral disease. The area under the ROC curve was 0.68. Patients were classified into one of four risk groups. We observed a good agreement between the observed and predicted survival probabilities for the four risk groups. The observed median survival durations were 7.5 (95% confidence interval [CI], 6.2 to 10.9), 13.4 (95% CI, 9.7 to 26.3), 18.9 (95% CI, 16.2 to 26.3), and 27.2 (95% CI, 21.9 to 42.8) months for the first, second, third, and fourth risk groups, respectively. The corresponding median predicted survival times were 8.8, 13.4, 17.4, and 22.80 for the four risk groups. CONCLUSION: This model could be used to predict individual survival probabilities and to stratify metastatic HRPC patients in randomized phase III trials.

Adenocarcinoma↗
PubMed2003

A randomized trial of aspirin to prevent colorectal adenomas in patients with previous colorectal cancer.

BACKGROUND: Experimental studies in animals and observational studies in humans suggest that regular aspirin use may decrease the risk of colorectal adenomas, the precursors to most colorectal cancers. METHODS: We conducted a randomized, double-blind trial to determine the effect of aspirin on the incidence of colorectal adenomas. We randomly assigned 635 patients with previous colorectal cancer to receive either 325 mg of aspirin per day or placebo. We determined the proportion of patients with adenomas, the number of recurrent adenomas, and the time to the development of adenoma between randomization and subsequent colonoscopic examinations. Relative risks were adjusted for age, sex, cancer stage, the number of colonoscopic examinations, and the time to a first colonoscopy. The study was terminated early by an independent data and safety monitoring board when statistically significant results were reported during a planned interim analysis. RESULTS: A total of 517 randomized patients had at least one colonoscopic examination a median of 12.8 months after randomization. One or more adenomas were found in 17 percent of patients in the aspirin group and 27 percent of patients in the placebo group (P=0.004). The mean (+/-SD) number of adenomas was lower in the aspirin group than the placebo group (0.30+/-0.87 vs. 0.49+/-0.99, P=0.003 by the Wilcoxon test). The adjusted relative risk of any recurrent adenoma in the aspirin group, as compared with the placebo group, was 0.65 (95 percent confidence interval, 0.46 to 0.91). The time to the detection of a first adenoma was longer in the aspirin group than in the placebo group (hazard ratio for the detection of a new polyp, 0.64; 95 percent confidence interval, 0.43 to 0.94; P=0.022). CONCLUSIONS: Daily use of aspirin is associated with a significant reduction in the incidence of colorectal adenomas in patients with previous colorectal cancer.

Adenoma↗
PubMed2003

Prognostic significance of reverse transcriptase polymerase chain reaction for prostate-specific antigen in metastatic prostate cancer: a nested study within CALGB 9583.

PURPOSE: To determine whether reverse transcriptase polymerase chain reaction (RT-PCR) to detect circulating prostate-specific antigen (PSA)-positive cells is a prognostic factor for survival in hormone refractory prostate cancer and to validate the prognostic importance of this test in relation to other known prognostic factors. PATIENTS AND METHODS: A single centralized laboratory received and analyzed whole blood for RT-PCR for PSA for a subset of patients enrolled on two Cancer and Leukemia Group B (CALGB) randomized trials (CALGB 9583 and CALGB 9480). Using 9583, a prognostic model was developed and an independent data set (CALGB 9480) was used to validate the fitted model. RESULTS: Of 162 patients in 9583, 91 (56%) patients were negative for RT-PCR for PSA and 71 (44%) patients were positive. The median survival time was 21 months (95% confidence interval [CI], 18 to 27 months) for RT-PCR-negative patients compared with 11 months (95% CI, 8 to 15 months) for RT-PCR-positive patients (P < or =.001). In multivariable analysis, the hazard ratio (HR) for death was 1.7 (95% CI, 1.2 to 2.4; P =.006) for positive RT-PCR patients compared with negative RT-PCR patients. A fitted model that incorporated RT-PCR for PSA and other factors was used to classify patients from 9480 into one of two risk groups: low or high. We observed good agreement between the observed and predicted survival probabilities for the two risk groups. CONCLUSION: RT-PCR to detect PSA-positive circulating cells is confirmed to be a significant prognostic factor of survival in patients with hormone refractory prostate cancer. This model could be used to stratify patients in randomized phase III trials.

Aged↗
PubMed2003

Analysis of survival data with missing measurements of a time-dependent binary covariate.

The objective of this study was to investigate the influence of the number and timing of a binary time-dependent covariate on the bias using the last-observation carried forward in the proportional hazards model. Under various assumptions of censoring rates, transition probabilities of the time-dependent covariate, sample size, and the log hazard-ratio for the covariate, we empirically examined the impact that the number and timing have on the bias of the estimator of the covariate. An example from the Systolic Hypertension in the Elderly Program was used. Inference on the effect of systolic blood pressure on survival is strongly affected by the number and timing of systolic blood measurements.

Humans↗
PubMed2002

Randomized study of three different doses of suramin administered with a fixed dosing schedule in patients with advanced prostate cancer: results of intergroup 0159, cancer and leukemia group B 9480.

PURPOSE: To test the hypothesis that the efficacy and toxicity of suramin in the treatment of patients with hormone-refractory prostate cancer was dose dependent. PATIENTS AND METHODS: Patients were randomized with equal probability to receive low-, intermediate-, or high-dose suramin (total doses 3.192, 5.320, and 7.661 g/m(2), respectively). Overall survival, time to progression, and response rate (prostate-specific antigen [PSA] and objective) for each treatment arm were compared. Relationships between plasma suramin concentrations and response, toxicity, and survival were also evaluated. RESULTS: Three hundred ninety patients were randomized. For the low-, intermediate-, and high-dose arms, the median survival time was 16, 14, and 13 months, respectively (P =.49). The objective response rate was 9%, 7%, and 15%, respectively (P =.10). PSA response rates were 24%, 28%, and 34%, respectively (P =.082). Landmark analyses of a 50% decline in PSA at 20 weeks showed a significant correlation with survival. There was a dose-response relationship between dose and toxicity. After adjusting for treatment arm, the measured suramin concentration was not associated with clinical response, PSA response, survival, or toxicity. CONCLUSION: Although high-dose suramin was associated with higher objective and PSA response rates, these were not statistically significant. Overall, no dose-response relationship was observed for survival or progression-free survival, but toxicity was increased with the higher dose. Patients treated with the low-dose level experienced modest toxicity, making it the preferred arm on this study. The lack of a dose-response relationship and the toxicity profile observed raise questions regarding the utility of suramin, particularly high-dose suramin, as administered on this schedule.

Aged↗
PubMed2002

Higher doses of mitoxantrone among men with hormone-refractory prostate carcinoma: a Cancer and Leukemia Group B study.

BACKGROUND: Mitoxantrone in combination with a low-dose glucocorticoid has been shown to produce more favorable outcomes among men with hormone-refractory prostate carcinoma than glucocorticoid alone. Therefore, the authors sought to determine the safety and activity of higher doses of mitoxantrone in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF) and a glucocorticoid in preparation for a possible Phase III trial comparing standard to dose-escalated mitoxantrone. METHODS: This Phase II trial enrolled 45 patients from October 1996 to March 1998. Twenty-one patients without pelvic irradiation (Arm I) received 21 mg/m(2) of mitoxantrone every 3 weeks, and 24 patients who had received pelvic irradiation (Arm II) were given 17 mg/m(2) on the same schedule. All patients received 40 mg of hydrocortisone in divided doses daily and GM-CSF at 500 microg/daily for a minimum of 10 days per cycle beginning on the third day of the cycle. RESULTS: In Arm I, 33% of assessable patients achieved a partial response, 50% had a > or = 50% decline in their PSA, and 35% had a > or = 75% decline in PSA values. The comparable numbers in Arm II were 24%, 48%, and 35%, respectively. The median survival times were 12 months in Arm I and 14 months in Arm II. Treatment had to be discontinued in 13% of patients because of thrombocytopenia. No other significant toxicities were encountered. CONCLUSIONS: Higher doses of mitoxantrone (17 and 21 mg/m(2)) were associated with activity comparable to many estramustine combinations and generally were well tolerated. However, because the degree and frequency of thrombocytopenia were greater than that observed with standard dose mitoxantrone (12-14 mg/m(2)), and because the median survival is apparently comparable to standard dose mitoxantrone, this approach to HRPC cannot be recommended for Phase III testing.

Aged↗
PubMed2002

Effects of a mammography decision-making intervention at 12 and 24 months.

BACKGROUND: Most women are not getting regular mammograms, and there is confusion about several mammography-related issues, including the age at which women should begin screening. Numerous groups have called for informed decision making about mammography, but few programs have resulted. Our research is intended to fill this gap. METHODS: We conducted a randomized controlled trial, which ran from 1997 to 2000. Women aged 40 to 44 and 50 to 54, who were enrolled in Blue Cross Blue Shield of North Carolina, were randomly assigned to one of three groups: usual care (UC), tailored print (TP) materials, or TP plus tailored telephone counseling (TP+TC). We assessed the impact of tailored interventions on knowledge about breast cancer and mammography, accuracy of breast cancer risk perceptions, and use of mammography at two time points after intervention-12 and 24 months. RESULTS: At 12 and 24 months, women who received TP+TC had significantly greater knowledge and more accurate breast cancer risk perceptions. Compared to UC, they were 40% more likely to have had mammograms (odds ratio=0.9-2.1). The effect was primarily for women in their 50s. TP had significant effects for knowledge and accuracy, but women who received TP were less likely to have had mammography. CONCLUSIONS: Decision-making interventions, comprised of two tailored print interventions (booklet and newsletter), delivered a year apart, with or without two tailored telephone calls, significantly increased knowledge and accuracy of perceived breast cancer risk at 12 and 24 months post-intervention. The effect on mammography use was significant in bivariate relationships but had a much more modest impact in multivariate analyses.

Adult↗
PubMed2002

Ovulation and ovarian cancer: a comparison of two methods for calculating lifetime ovulatory cycles (United States).

OBJECTIVE: To compare two methods for calculating lifetime ovulatory cycles (LOC) to determine if more detailed menstrual cycle information results in stronger associations with ovarian cancer. METHODS: Using data from 232 cases and 242 controls in a population-based study of ovarian cancer, we compared a standard method for calculating LOC with a second method that had more detailed information on menstrual characteristics. Odds ratios for ovarian cancer by number of LOC were estimated using unconditional logistic regression. RESULTS: The average number of LOC was 29 fewer for the second method that had more detailed menstrual cycle information, as compared to the standard method (p < 0.0001). The difference was due primarily to the second method considering episodes of missed/irregular periods. Associations between LOC and ovarian cancer were weaker for the second method than the standard method. Further analyses suggested that a reduced number of ovulatory cycles due to menstrual irregularity was associated with increased ovarian cancer risk, in contrast to the protective effects observed for fewer ovulatory cycles due to pregnancy or oral contraceptive use. CONCLUSION: Obtaining additional details on menstrual factors that affect LOC, particularly missed or irregular cycles, provides important information on ovarian cancer risk. Our data suggest that episodes of anovulation due to menstrual disturbances should be evaluated separately from anovulation due to pregnancy or oral contraceptive use.

Case-Control Studies↗
PubMedDate not supplied

9-Nitrocamptothecin as second line chemotherapy for men with progressive, metastatic, hormone refractory prostate cancer: Results of the CALGB 99901.

BACKGROUND: Institution of early hormone therapy in the PSA era coupled with demonstration of clinical benefit with chemotherapy in hormone refractory prostate cancer (HRPC) and acceptance of PSA decline as a surrogate for response has resulted in introduction of chemotherapy earlier in the natural history of disease. There now exists a need to identify, effective agents for second line chemotherapy. 9-nitrocamptothecin (9-NC) a novel, oral camptothecin analogue was tested as second line chemotherapy for patients with progressive hormone refractory prostate cancer. PATIENTS AND METHODS: Eligible patients had metastatic hormone refractory prostate cancer with performance status (0-1) following progression on at least 1 prior cytotoxic chemotherapy. 9-NC was administered orally at the dose of 1.5 mg/m2/d for 5 days each week for 3 weeks, followed by rest for 1 week. Response was evaluated after 2 cycles according to the guidelines set forth for Phase II trials in HRPC by the PSA working group. RESULTS: Thirty-five patients were recruited to the study within a period of 6 months; 33 were evaluable for analysis. No patients had a >50% decline in PSA levels. Two out of 8 (25%) patients with measurable disease and 5/25 (20%) patients with nonmeasurable disease showed stable disease. The median time to disease and PSA progression was 2 months [95% confidence interval (CI), 0.9-2.8]. The median overall survival was 10 months (95% CI = 5-12). Seven patients are alive after a median follow-up of 23 months. CONCLUSIONS: 9-nitrocamptothecin failed to elicit clinical or PSA responses. Further study in pretreated HRPC patients is not warranted.

Administration, Oral↗