Sunitinib maintenance therapy after response to docetaxel in metastatic castration resistant prostate cancer (mCRPC).

Background Docetaxel is a standard first-line treatment option for men with metastatic castration resistant prostate cancer (mCRPC). Sunitinib is attractive as a maintenance therapy due to its mechanism of action, oral route of administration, and acceptable toxicity profile. We designed a phase II study of sunitinib in patients with mCRPC who responded to docetaxel. Methods Patients with responding or stable disease at the completion of docetaxel treatment received 50 mg of sunitinib on 4 week on 2 week off cycles. Treatment continued until disease progression (either by RECIST 1.1 criteria or by cancer related symptomatic progression), intolerable toxicity, start of new cancer therapy, withdrawal of consent, or death. The primary endpoint was progression free survival. Secondary endpoints included PSA response rate and safety. Results Twenty-three patients were enrolled and treated. The mean number of prior cycles of docetaxel given was 8.6 (range 4-12). The median number of cycles of sunitinib administered was 4 (range 1-11). Adverse events were generally grade 1-2 with 12 % grade ≥ 3 which were of a type and severity expected for sunitinib. Median PFS was 4.4 months (95 % CI: 1.6-5.1). Most patients had immediate PSA increases without other evidence of disease progression, with the mean increases in PSA over baseline being 197 %, 342 %, and 1437 % in Cycles 1, 2, and 3, respectively. Conclusion Sunitinib was tolerable as maintenance therapy but median PFS was significantly lower than the predefined threshold of 6 months.

Rural and small town breast cancer survivors' preferences for physical activity.

BACKGROUND: Recent data suggests that only 35 % of rural and small town breast cancer survivors are achieving physical activity (PA) guidelines after treatment. PURPOSE: The purpose of this study was to determine preferences for PA counseling and programming and barriers to program participation in a sample of rural and small town breast cancer survivors. METHODS: Survivors (n = 524) residing in rural and small town areas of Alberta, Canada completed a mailed self-report survey that assessed demographic variables, PA, and PA counseling and programming preferences. RESULTS: Seventy-eight percent of survivors indicated they would have possibly (i.e., yes or maybe) been interested in being counseled about PA at the time of diagnosis, while 70 % would possibly be interested in being counseled about PA at this current time. Overall, 85 % felt they would possibly be able to participate in a PA program. Receiving chemotherapy was negatively associated with wanting to receive PA counseling (odds ratio [OR] = 0.58; 95 % confidence interval [CI], 0.39 to 0.86), PA program interest (OR = 0.43; 95 % CI, 0.28 to 0.67), and PA program ability (OR = 0.44; 95 % CI, 0.26 to 0.75). Preferred activities involved walking (51 %), flexibility and related activities (e.g., yoga, stretching) (36 %), and strength training (27 %). CONCLUSIONS: Rural and small town survivors appear to be interested in and able to participate in PA counseling and programs. PA initiatives targeted to the preferences of breast cancer survivors living in nonurban areas may be more likely to facilitate and maintain PA behavior.

Predictors of physical activity among rural and small town breast cancer survivors: an application of the theory of planned behaviour.

The primary objective of this study was to investigate the utility of the two-component theory of planned behaviour (TPB) in understanding physical activity intentions and behaviour in rural and small town breast cancer survivors. The secondary objective was to elicit the most common behavioural, normative and control beliefs of rural and small town survivors regarding physical activity. Using a cross-sectional survey design, 524 rural and small town breast cancer survivors completed a mailed survey that assessed physical activity and TPB variables. Physical activity intention explained 12% of the variance in physical activity behaviour (p < 0.01) while the TPB constructs together explained 43% of the variance in physical activity intention (p < 0.01). Unique behavioural, normative and control beliefs were elicited from the sample. The two-component TPB framework appears to be a suitable model to initiate an understanding of physical activity determinants among rural and small town breast cancer survivors. These data can be used in the development and establishment of physical activity behaviour interventions and health promotion materials designed to facilitate physical activity behaviour among rural and small town breast cancer survivors.

Physical activity is associated with clinically important differences in health-related quality of life among rural and small-town breast cancer survivors.

PURPOSE: The primary purpose of this study was to examine differences in health-related quality of life and fatigue between rural and small-town (RST) breast cancer survivors meeting and not meeting public health physical activity (PA) recommendations. METHODS: Using a retrospective survey design, RST breast cancer survivors (N = 524) residing in Southern Alberta, Canada completed a mailed questionnaire assessing self-reported prediagnosis, on treatment, and current PA behavior, and current health-related quality of life and fatigue. RESULTS: Analyses indicated 44.1%, 13.7%, and 34.7% of RST breast cancer survivors met public health PA recommendations during prediagnosis, on treatment, and post-treatment (i.e., current) time periods, respectively. Multivariate analyses of variance suggested indicated survivors currently meeting PA recommendations reported clinically advantageous differences in health-related quality of life and fatigue symptoms than survivors not currently meeting PA recommendations. Repeated measures analyses also indicated significant differences in PA behavior across the three cancer-related time periods (all p < 0.01). CONCLUSIONS: The results of this study provide evidence that RST breast cancer survivors have similar PA behavior estimates across the cancer trajectory to urban survivors. Being physically active was associated with clinically important advantages with respect to health-related quality of life and fatigue. Strategies designed to facilitate PA behavior in the RST breast cancer survivor population are warranted.

Randomized trial of two intravenous schedules of the topoisomerase I inhibitor liposomal lurtotecan in women with relapsed epithelial ovarian cancer: a trial of the national cancer institute of Canada clinical trials group.

PURPOSE: Liposomal lurtotecan (OSI-211) is a liposomal formulation of the water-soluble topoisomerase I inhibitor lurtotecan (GI147211), which demonstrated superior levels of activity compared with topotecan in preclinical models. We studied two schedules of OSI-211 in a randomized design in relapsed ovarian cancer to identify the more promising of the two schedules for further study. PATIENTS AND METHODS: Eligible patients had measurable epithelial ovarian, fallopian, or primary peritoneal cancer that was recurrent after one or two prior regimens of chemotherapy. Patients were randomly assigned to receive either arm A (OSI-211 1.8 mg/m(2)/d administered by 30-minute intravenous infusion on days 1, 2, and 3 every 3 weeks) or arm B (OSI-211 2.4 mg/m(2)/d administered by 30-minute intravenous infusion on days 1 and 8 every 3 weeks). The primary outcome measure was objective response, which was confirmed by independent radiologic review, and a pick the winner statistical design was used to identify the schedule most likely to be superior. RESULTS: Eighty-one patients were randomized between October 2000 and September 2001. The hematologic toxic effects were greater on arm A than on arm B (grade 4 neutropenia, 51% v 22%, respectively), as was febrile neutropenia (26% v 2.4%, respectively). Of the 80 eligible patients, eight patients (10%) had objective responses; six responders (15.4%; 95% CI, 6% to 30%) were in arm A and two responders (4.9%; 95% CI, 1% to 17%) were in arm B. CONCLUSION: The OSI-211 daily for 3 days intravenous schedule met the statistical criteria to be declared the winner in terms of objective response. This schedule was also associated with more myelosuppression than the schedule of OSI-211 administered in arm B.

Effect of protease inhibitor-based highly active antiretroviral therapy on survival in HIV-associated advanced Kaposi's sarcoma patients treated with chemotherapy.

OBJECTIVE: To determine whether the use of protease inhibitor (PI)-based antiretroviral (ARV) therapy had an impact on the survival of patients with human immunodeficiency virus (HIV) infection-associated Kaposi's sarcoma (KS) who were receiving systemic chemotherapy. METHOD: Records of 48 AIDS patients with extensive KS who received chemotherapy from 1995 to 1999 were reviewed. Analysis by presence or absence of PI treatment was undertaken, and patients who were receiving nonnucleoside reverse transcriptase inhibitors (NNRTIs) were excluded from the analysis. RESULTS: Median age was 38 years, and 47 patients were men having sex with men. Half of the patients (54%) had at least one prior AIDS-defining event. Median CD4 count at diagnosis of KS was 28 cells/microL (range, 1-625). Visceral KS was present in 33 patients (69%), and the remainder of patients had extensive and symptomatic cutaneous and/or mucous membrane involvement. All patients received at least one cycle of chemotherapy, including vincristine/bleomycin or an anthracycline-containing regimen. There was a significant difference in the median survival (MS) between the 28 patients (58%) treated with PI-based antiretroviral therapy (31 months [range, 1.8-48]) and the group not receiving PI (7 months [range, 1-28], p =.0001). In addition, 81% of patients in the PI group were alive at 18 months from initiation of chemotherapy versus 12% in the non-PI group. Twenty patients (71%) in the PI-treated group were able to discontinue chemotherapy for at least 1 month after remission of KS, in comparison to 3 of 20 (15%) patients in the group of patients who did not receive PI (p =.00001). Death due to KS occurred in 6 of 28 (21%) patients (total 9 deaths) in the PI group and 14 of 20 (70%) patients (total 18 deaths) in the non-PI group (p =.001). CONCLUSION: In a nonselected group of patients with advanced and extensive KS in a real-life clinical setting, our results show a survival benefit and a decrease in KS-related death for patients receiving chemotherapy and PI-based ARV therapy when compared to patients not receiving PI-based therapy. Discontinuation of chemotherapy in patients receiving PI-based antiretroviral therapy appears to be feasible in patients who attain remission of KS.

A phase II trial of JM-216 in cervical cancer: an NCIC CTG study.

OBJECTIVE: BMS-182751 (JM-216) is an orally bioavailable platinum compound with activity in platinum-sensitive and platinum-resistant preclinical models. The objective was to determine its activity in recurrent/metastatic squamous cell carcinoma of the cervix. METHODS: We conducted a phase II study of BMS-182751 given at a dose of 30 mg/m(2) daily for 14 days every 5 weeks. RESULTS: Eighteen patients (pts) with advanced/recurrent squamous cancer of the cervix not amenable to curative therapy with measurable disease who had received no prior chemotherapy for systemic disease were entered, all of whom are evaluable for response and toxicity. Median age was 47 years (35-74 years); all pts had received prior pelvic irradiation (RT); 4 pts had received cisplatin as adjustment therapy with radiation; PS was 0 (6 pts), 1 (7 pts), and 2 (5 pts); sites of disease included nodes (10 pts), pelvis (5 pts), lung (4 pts), and bone (3 pts). Median number of cycles was two (1-6) with 8 pts receiving three or more cycles. Toxicity was modest and usually grade 1 or 2 in severity with the most frequent drug related toxicity being nausea (56%), fatigue (50%), anorexia (39%), diarrhea (39%), vomiting (39%), constipation (28%), and altered taste (22%). Six pts had grade 3 or 4 granulocytopenia and only 1 pt, grade 3 or 4 thrombocytopenia. Two pts had grade 2 or 3 creatinine increases. There were no treatment-related deaths. One pt with a treatment-free interval of 30 years achieved a partial response, while 12 pts had a best response of stable disease. CONCLUSIONS: BMS-182751 is generally well tolerated, but has limited activity in pts with recurrent cervical cancer.