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Biosimilars are biologic products that are highly similar, but not identical, to a licensed reference (or "originator") biologic product. These agents have the potential to provide efficiencies and improve access to treatment for patients. Biosimilars are currently available for use in clinical practice, including oncology indications, and several more are in clinical development. Due to several key differences in their fundamental properties, production and manufacturing of biosimilars is more complex compared with that of small-molecule generic drugs. Accordingly, the generic drug approval process is not suitable or transferable to biosimilars, the approval of which involves extensive and thorough comparison with the originator biologic. Advanced practice providers play an important role in evaluating treatment options available to patients, prescribing, patient education, and product monitoring. In order to perform these tasks effectively, advanced practice providers should understand the concepts related to biosimilars in clinical practice, particularly regarding extrapolation to other indications, product labeling, interchangeability between products, and routine pharmacovigilance, among other clinical considerations. However, many health-care providers have limited awareness and minimal experience regarding biosimilars. Thus, the purpose of this review is to provide an overview of biosimilars and discuss the clinical considerations for oncology advanced practice providers concerning these therapies.

Purpose/Objective(s) We sought to assess the utility of docetaxel administered concurrently with salvage radiation therapy (SRT) following postprostatectomy biochemical failure (BF). Methods and materials Men with postprostatectomy BF were accrued on a single-arm phase 2 clinical trial. SRT doses ranged from 64.8 to 70.2 Gy and were delivered in 1.8-Gy fractions to the prostate bed alone as the clinical target volume with a +1-cm uniform planning target volume expansion. The primary endpoint was progression-free survival at 4 years compared with the Stephenson nomogram estimate. Kaplan-Meier methods were used to assess late toxicity, BF, and distant metastases. An unplanned matched-pair analysis was performed with 19 patients treated with SRT alone. Results Nineteen men were accrued and treated. Median follow-up was 4.8 years. Median pre-RT prostate-specific antigen level was 0.7 ng/mL (interquartile range, 0.4-1.3 ng/mL). All 8 cycles of docetaxel were completed in 17 (89%) patients. Acute grade 1-4 toxicities were observed in 79%, 50%, 58%, and 11%, respectively. A total of 68% of acute grade 1 toxicities were related to fatigue, urinary, or bowel symptoms. For grade 2 toxicities, 76% were related to neutropenia, fatigue, or urinary symptoms. Acute grade 3 and 4 toxicities were most commonly neutropenia (84% and 100%, respectively). All late toxicities were grade 1 to 2 with 89% related to bowel or urinary function. Predicted 4-year progression-free survival was 39% and observed was 42% (90% confidence interval [CI], 24-60). Matched-pair analysis demonstrated no significant improvement in BF ( P = .96, hazard ratio, 0.98; 90% CI, 0.4-2.3) or distant metastases ( P = .09; hazard ratio, 0.3; 90% CI, 0.07-1.2), and no difference between late bowel ( P = .60) or urinary toxicity ( P = .41). Conclusions Docetaxel can safely be administered concurrently with SRT without significantly impacting posttreatment toxicity. Neutropenia was the most significant acute toxicity. Given the small sample size, no clear clinical benefit was observed. Larger studies are needed to determine the efficacy of concurrent docetaxel in this setting.

Background: Primary care providers inevitably care for prostate cancer survivors. However, few comprehensive resources exist to aid them in providing the most up-to-date and evidence-based care. To meet this clinical need, we examined and updated the Michigan Cancer Consortium prostate cancer survivorship guidelines. Methods: Using an expert panel and focus groups comprised of prostate cancer stakeholders, we updated the Michigan Cancer Consortium's 2009 Guidelines for the Primary Care Management of Prostate Cancer Post-Treatment Sequelae. Results: The guideline recommendations were modified to serve as a point-of-care resource and to facilitate care transitions between specialty and primary care. The modified recommendations were approved by the Michigan Cancer Consortium and now include the following elements: (1) patient-reported symptom assessment, (2) distinctions between medical and self-management strategies for prostate cancer treatment-related side effects, (3) recommendations for involv...

BACKGROUND: After external beam radiation therapy (EBRT) for prostate cancer, a short interval to biochemical failure of

BACKGROUND The current study evaluated the efficacy of oral uracil/tegafur (UFT) and leucovorin (LV) in patients with hormone-refractory metastatic prostrate carcinoma. METHODS Twenty-eight patients with hormone-refractory metastatic carcinoma of the prostate who had undergone antiandrogen withdrawal and no more than 1 prior chemotherapy treatment were enrolled on a single-institution Phase II trial. Patients were treated with oral UFT at a dose of 300 mg/m2/d and oral LV at a dose of 90 mg/day for 28 days followed by 7 days off therapy on a 35-day cycle regimen. RESULTS Twenty-six patients were evaluable for response and toxicity. There was no response by objective criteria in 9 patients with measurable disease. Four responses by prostate-specific antigen (PSA) criteria (i.e., PSA decrease by > 50%) were noted (15%) lasting a mean of 20.5 weeks. Therapy was generally well tolerated, with 2 patients developing Grade 4 toxicity (1 patient each with diarrhea and hand-foot syndrome) and 4 patients having significant Grade 3 toxicity (anemia, hyperbilirubinemia, and vomiting) (Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria). Six patients had stable disease by clinical, laboratory, and radiologic criteria for an average of 5 cycles of treatment (25 wks). CONCLUSIONS Although UFT and LV are generally well tolerated in the setting of hormone-refractory metastatic prostate carcinoma, the combination has a low level of activity. Its toxicity and activity is similar to that observed when intravenous 5-fluorouracil or capecitabine are given alone. It may be an option for further investigations in combination regimens. Cancer 2006. © 2006 American Cancer Society.

The pliability of cancer cells to mutate into several different phenotypes in an attempt to find one that will survive and colonize at the metastatic site is a tremendous "hurdle" to overcome in designing novel cancer therapeutics. New targets of therapy are essential if we are to effectively overcome the evasiveness of cancer. The interaction between the tumor cell and the surrounding microenvironment creates a vicious cycle that perpetuates disease survival and progression. The future of cancer therapy resides in the ability to focus on the recruited and exploited relationships of the cancer cell with the host environment. These therapies target cancer cell growth early and interrupt the vicious cycle that is created by the tumor cells interacting with bone components by inhibiting osteoclasts, osteoblasts, stromal cells, and endothelial cells. They alter the bone microenvironment, creating a hostile "soil" that prevents the "seed" from developing into bone metastases and represent a potential new platform for the development of prostate cancer therapeutics.

Background Low-risk prostate cancer (PCa) patients have excellent outcomes, with treatment modality often selected by perceived effects on quality of life. Acute urinary symptoms are common during external beam radiotherapy (EBRT), while chronic symptoms have been linked to urethral dose. Since most low-risk PCa occurs in the peripheral zone (PZ), we hypothesized that EBRT using urethral sparing intensity modulated radiation therapy (US-IMRT) could improve urinary health-related quality of life (HRQOL) while maintaining high rates of PCa control. Methods Patients with National Comprehensive Cancer Network (NCCN) defined low-risk PCa with no visible lesion within 5 mm of the prostatic urethra on MRI were randomized to US-IMRT or standard (S-) IMRT. Prescription dose was 75.6 Gy in 41 fractions to the PZ + 3–5 mm for US-IMRT and to the prostate + 3 mm for S-IMRT. For US-IMRT, mean proximal and distal urethral doses were limited to 65 Gy and 74 Gy, respectively. HRQOL was assessed using the Expanded Prostate Cancer Index (EPIC) Quality of Life questionnaire. The primary endpoint was change in urinary HRQOL at 3 months. Results From June 2004 to November 2006, 16 patients were randomized, after which a futility analysis concluded that continued accrual was unlikely to demonstrate a difference in the primary endpoint. Mean change in EPIC urinary HRQOL at 3 months was −0.5 ± 11.2 in the US-IMRT arm and +3.9 ± 15.3 in the S-IMRT arm (p = 0.52). Median PSA nadir was higher in the US-IMRT arm (1.46 vs. 0.78, p = 0.05). At 4.7 years median follow-up, three US-IMRT and no S-IMRT patients experienced PSA failure (p = 0.06; HR 8.8, 95% CI 0.9–86). Two out of 3 patients with PSA failure had biopsy-proven local failure, both located contralateral to the original site of disease. Conclusions Compared with S-IMRT, US-IMRT failed to improve urinary HRQOL and resulted in higher PSA nadir and inferior biochemical control. The high rate of PSA failure and contralateral local failures in US-IMRT patients, despite careful selection of MRI-screened low-risk patients, serve as a cautionary tale for focal PCa treatments.

Dural metastases have traditionally been considered a rare complication of prostate cancer; various case reports and autopsy series from the past have shown rates between 1 and 9%. Recent data from our advanced prostate cancer autopsy series, however, demonstrate a rate of dural lesions around 25%, suggesting that such complications may be more prevalent than previously reported. A case of prostate cancer, which was diagnosed after the patient presented with visual changes, is reported. Subsequent work-up revealed a lesion in the left tentorium, which was determined to be adenocarcinoma and stained positive for PSA and PAP.

BACKGROUND The primary objective of the current study was to identify the tolerable dose level of oral vinorelbine when given in combination with estramustine to men with hormone-refractory prostate cancer (HRPC). The secondary objectives were to describe the toxicities of the combined regimen in patients with HRPC and to estimate the efficacy of oral vinorelbine in combination with estramustine based on the prostate-specific antigen (PSA) response. METHODS Thirty-three patients with HRPC were treated on a 28-day cycle with estramustine at a dose of 140 mg orally 3 times a day on Days 1-3 and 8-10. Vinorelbine was given orally on Days 2 and 9. The initial dose of vinorelbine was 50 mg/m2 and was escalated to 70 mg/m2 using the time-to-event continual reassessment method. RESULTS Three of 17 patients experienced dose-limiting toxicity at the 70 mg/m2 dose level of oral vinorelbine. One patient experienced dose-limiting toxicity at a dose of 60 mg/m2 and no dose-limitig toxicities were reported at the 50 mg/m2 dose. The overall response rate by ≥50% reduction in PSA was 17.2%, (95% confidence interval, 5.9-35.8%). CONCLUSIONS Oral vinorelbine at doses of 70 mg/m2 may be safely combined with estramustine. The combination appears to have modest activity in men with advanced prostate cancer. The trial design employed the time-to-event continual reassessment method, which potentially allows for rapid accrual, a more complete assessment of toxicities, and a larger fraction of patients to be treated at an effective dose. More active regimens are needed to further evaluate the utility of this clinical trial design in patients with prostate cancer. Cancer 2006. © 2006 American Cancer Society.

The case of a 66-year-old gentleman who presented with unilateral proptosis, eye pain and partial loss of vision seven years after his original prostate cancer diagnosis is reported. MRI of the orbits revealed a 2-cm lesion in the posterolateral right orbital wall near the optic foramen with compression of the optic nerve. Metastatic orbital lesions are relatively uncommon in prostate cancer. Treatment is palliative and varies according to the time of presentation in the course of the disease. This patient's symptoms resolved after reinitiation of combined androgen blockade.

BACKGROUND The authors evaluated the combination of oral cyclophosphamide, oral prednisone, and diethylstilbestrol (DES) in patients with androgen-independent prostate carcinoma (AIPC). METHODS Thirty-seven patients with prostate carcinoma refractory to androgen ablation who had undergone antiandrogen withdrawal (if previously treated with an antiandrogen) were enrolled in the current study. They were treated with oral cyclophosphamide 100 mg per day on Days 1–20, prednisone 10 mg per day continuously, and DES 1 mg continuously, on a 30-day cycle. Warfarin 1 mg per day was given as prophylaxis for thrombosis. Patient levels of prostate-specific antigen (PSA) were monitored on a monthly basis, with imaging studies every 3 months. Patients continued to receive therapy until disease progression or the occurrence of significant toxicity. The effect of therapy on the patient's quality of life was assessed using the Functional Assessment of Cancer Therapy–Prostate. RESULTS Thirty-six patients were evaluable for response. Of the 36 patients, 15 (42%) had a 50% or greater decline in PSA levels from pretreatment levels and 1 patient (6%) with measurable disease had a partial response to therapy. The median duration of response was 4.5 months (range, 4–18 months). The overall median survival period was 16.4 months. The treatment was well tolerated, with only three patients removed from the study for toxicities associated with treatment. One patient, who had been treated for more than 24 months, developed acute leukemia. Quality of life evaluation in 17 patients showed a significant improvement in responders, whereas nonresponders had no deterioration while receiving therapy. CONCLUSIONS Cyclophosphamide, prednisone, and DES represent a well tolerated, low-cost combination therapy with significant activity in the treatment of patients with AIPC. Cancer 2003. © 2003 American Cancer Society. DOI 10.1002/cncr.11686

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