Background
The cyclooxygenase-2 (COX-2) enzyme plays a major role in tumor progression and resistance to chemotherapy. A Phase-II study was undertaken to determine the activity of a dose attenuated ...schedule of irinotecan, capecitabine, and the COX-2 inhibitor celecoxib in patients with advanced colorectal cancer.
Methods
The eligibility criteria included a pathologically or cytologically confirmed diagnosis of adenocarcinoma of the colon or rectum that was metastatic. Patients received a combination of irinotecan 70 mg/m
2
over 30 min I.V. on days 1 and 8, capecitabine 1,000 mg/m
2
twice per day orally on days 1–14, and celecoxib at a daily dose of 800 mg continuously. Cycles were repeated every 21 days.
Results
Fifty-one patients were enrolled (median age 58 years; M : F 31 : 20). The objective response rate was 21/51 = 41% 95% confidence intervals (CI), 0.28–0.55. The median time to progression was 7.7 months (95% CI, 6.2–8.6 months). Median survival time and probability of survival at 1 year were 21.2 months (95% CI, 13.8–n/a), and 75% (95% CI, 0.63–0.88), respectively. The major toxicity was Grade 3 or 4 diarrhea, seen in 24 and 10% of patients, respectively. There were no treatment related deaths.
Conclusions
The lower dose intensity of irinotecan appeared to maintain activity and improve tolerability when combined with capecitabine. The addition of celecoxib to irinotecan and capecitabine did not appear to significantly increase the activity of this doublet based on the RECIST criteria for objective response.
Early chemohormonal therapy in metastatic prostate cancer may offer an advantage by simultaneously targeting androgen-dependent and -independent clones. Hence, a phase II trial was conducted to ...evaluate the efficacy and toxicity of estramustine and etoposide in hormone-sensitive metastatic prostate cancer.
Eligibility consisted of untreated metastatic prostate cancer, adequate organ function, and a performance status of 0 to 2 by Zubrod criteria. A 21-day schedule of oral estramustine (10 mg/kg/day) and etoposide (50 mg/m2/day) was administered every 28 days. Hormonal therapy was allowed at the end of the protocol therapy. Toxicity was assessed weekly, PSA levels were assessed with each cycle, and objective response was evaluated every 3 cycles.
Twenty-one patients were enrolled (10 white, 11 black) with a median age of 59.5 years (range, 42-79 years), a median PSA of 338 ng/mL (range, 0.9-20,000 ng/mL), and a median Gleason score of 8 points. Ten patients had bone-only metastases, 11 had measurable disease, of whom 4 had visceral metastases. A total of 128 cycles were administered (median, 6 cycles). No dose reductions were required. Nineteen patients were able to be evaluated for response. Severe toxicities included thromboembolic events and anemia in 2 patients each and fatigue in 1 patient. There were no episodes of febrile neutropenia. Response was observed in 8 of 11 patients (73%) with measurable disease. Median PSA nadir after therapy was 0.45 ng/mL, and undetectable PSA (<0.1 ng/mL) was achieved in 4 patients. Median time to PSA progression was 16.65 months. At a median follow-up of 34 months, 18 patients were alive. The 1-, 2-, and 3-year overall survival rates were 90%, 82%, and 72% respectively. Median survival has not yet been reached.
The combination of estramustine and etoposide is well tolerated, and has promising activity in newly diagnosed metastatic prostate cancer.
Introduction/Background. Nonmetastatic castrate resistant prostate cancer (CRPC) is a challenging disease state. The objective of this study was to evaluate the efficacy and tolerability of ...bevacizumab in nonmetastatic CRPC patients. Patients. Patients with prostate cancer who developed PSA recurrence after local therapy were included if they had absence of bone or visceral metastases and PSA progression despite androgen deprivation therapy. Methods. Bevacizumab 10 mg/kg intravenously was administered every 14 days until PSA progression, development of metastasis, or unacceptable toxicity. Results. 15 patients were enrolled and treated with bevacizumab for a median duration of 3.1 months. Median baseline PSA was 27 ng/mL, and seven patients had Gleason Score ≥8. Five patients had declined in PSA during the treatment. Median PSA doubling time was prolonged from 4.7 months pretreatment to 6.5 months. Median time to PSA progression and new metastasis were 2.8 and 7.9 months, respectively. There were three grade 3 adverse events (one proteinuria and two hypertension) and one pulmonary embolism. There was no treatment-related mortality. Conclusion. Bevacizumab therapy had minimal impact on the disease course of nonmetastatic CRPC, and investigation of novel strategies is needed.
High-risk prostate cancer is a heterogeneous group that includes patients with clinically locally advanced stage disease at diagnosis. Unlike overt locally advanced disease, prediction of risk in ...clinically localized disease at an individual patient level, is not always easy or accurate with present knowledge. Gleason score, pretreatment prostate specific antigen (PSA), and stage (capsular invasion, seminal vesicle and nodal involvement) are the universally recognized criteria used to define risk. Overall, this group of patients have a greater than 50% risk of relapse. Historically, local treatment modalities with radical prostatectomy or radiation therapy constituted the mainstay of therapy in the majority of localized prostate cancer patients. However, the primary cause of failure and disease mortality stems from the development of systemic metastases. As we continue to witness stage migration towards earlier stage disease (presumably PSA related) and mortality reduction, devising better strategies for cure is a must. Recently completed randomized trials indicate a benefit from the use of hormonal therapy in patients with locally advanced prostate cancer treated with radiation therapy or node positive patients, post radical prostatectomy. While hormone-based combined modality trials have consistently shown improvements in local and systemic disease control, only two of these demonstrated improvements in overall survival. The palliative benefit of chemotherapy in hormone refractory disease and the promising response rates with newer agents has evoked interest in the use of chemotherapy in high-risk prostate cancer in the adjuvant and neoadjuvant settings. Several phase II and III trials are ongoing. Novel avenues of therapy such as tyrosine kinase inhibitors, gene therapy and angiogenesis inhibitors incorporated in a multimodality treatment strategy are likely to impact the course of this disease in the future.
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