OC-0511 Urethra and bladder dose-effect relations for genitourinary toxicity after EBRT for prostate cancer

AbstractAndrogen deprivation therapy (ADT) used for prostate cancer (PCa) management is associated with metabolic and anthropometric toxicity. Metformin given concurrent to ADT is hypothesized to counteract these changes. This planned interim analysis reports the gastrointestinal and genitourinary toxicity profiles of PCa patients receiving ADT and prostate/pelvic radiotherapy plus metformin versus placebo as part of a phase 2 randomized controlled trial. Men with intermediate or high-risk PCa were randomized 1:1 to metformin versus placebo. Both groups were given ADT for 18–36 months with minimum 2-month neoadjuvant phase prior to radiotherapy. Acute gastrointestinal and genitourinary toxicities were quantified using CTCAE v4.0. Differences in ≥ grade 2 toxicities by treatment were assessed by chi-squared test. 83 patients were enrolled with 44 patients randomized to placebo and 39 randomized to metformin. There were no significant differences at any time point in ≥ grade 2 gastrointestinal toxicities or overall gastrointestinal toxicity. Overall ≥ grade 2 gastrointestinal toxicity was low prior to radiotherapy (7.9% (placebo) vs. 3.1% (metformin), p = 0.39) and at the end of radiotherapy (2.8% (placebo) vs 3.1% (metformin), p = 0.64). There were no differences in overall ≥ grade 2 genitourinary toxicity between treatment arms (19.0% (placebo) vs. 9.4% (metformin), p = 0.30). Metformin added to radiotherapy and ADT did not increase rates of ≥ grade 2 gastrointestinal or genitourinary toxicity and is generally safe and well-tolerated.

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Randomized Trial of Hypofractionated, Dose-Escalated, Intensity-Modulated Radiation Therapy (IMRT) Versus Conventionally Fractionated IMRT for Localized Prostate Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2018.77.9868 ◽

2018 ◽

Vol 36 (29) ◽

pp. 2943-2949 ◽

Cited By ~ 35

Author(s):

Karen E. Hoffman ◽

K. Ranh Voong ◽

Lawrence B. Levy ◽

Pamela K. Allen ◽

Seungtaek Choi ◽

...

Keyword(s):

Prostate Cancer ◽

Radiation Therapy ◽

Randomized Trial ◽

Intensity Modulated Radiation Therapy ◽

Cancer Control ◽

Localized Prostate Cancer ◽

Intensity Modulated ◽

Genitourinary Toxicity ◽

Gi Toxicity ◽

Conventionally Fractionated

Purpose Hypofractionated radiotherapy delivers larger daily doses of radiation and may increase the biologically effective dose delivered to the prostate. We conducted a randomized trial testing the hypothesis that dose-escalated, moderately hypofractionated intensity-modulated radiation therapy (HIMRT) improves prostate cancer control compared with conventionally fractionated IMRT (CIMRT) for men with localized prostate cancer. Patients and Methods Men were randomly assigned to 75.6 Gy in 1.8-Gy fractions delivered over 8.4 weeks (CIMRT) or 72 Gy in 2.4 Gy fractions delivered over 6 weeks (HIMRT, biologically equivalent to 85 Gy in 1.8-Gy fractions assuming prostate cancer α-to-β ratio of 1.5). Failure was defined as prostate-specific antigen (PSA) failure (nadir plus 2 ng/mL) or initiation of salvage therapy. Modified Radiation Therapy Oncology Group criteria were used to grade late (≥ 90 days after completion of radiotherapy) GI and genitourinary toxicity. Results Most of the 206 men (72%) had cT1, Gleason score 6 or 7 (99%), and PSA level ≤ 10 ng/mL (90%) disease. Androgen deprivation therapy was received by 24%. With a median follow-up of 8.5 years, men treated with HIMRT experienced fewer treatment failures (n = 10) than men treated with CIMRT (n = 21; P = .036). The 8-year failure rate was 10.7% (95% CI, 5.8% to 19.1%) with HIMRT and 15.4% (95% CI, 9.1% to 25.4%) with CIMRT. There was no difference in overall survival ( P = .39). There was a nonsignificant increase in late grade 2 or 3 GI toxicity with HIMRT (8-year 5.0% v 12.6%; P = .08). However, GI toxicity was only 8.6% when rectal volume receiving 65 Gy of HIMRT was ≤ 15%. Late genitourinary toxicity was similar ( P = .84). There was no grade 4 toxicity. Conclusion The results of this randomized trial demonstrate superior cancer control for men with localized prostate cancer who receive dose-escalated moderately hypofractionation radiotherapy while shortening treatment duration.

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2: Acute and Subacute Gastrointestinal and Genitourinary Toxicity Profiles of Metformin Versus Placebo Plus Prostate and Pelvic Radiotherapy for the Management of High Risk Prostate Cancer: Interim Toxicity Results of a Double-Blinded, Multicentre, Phase Ii Randomized Controlled Trial

Radiotherapy and Oncology ◽

10.1016/s0167-8140(20)30894-x ◽

2020 ◽

Vol 150 ◽

pp. S4-S5

Author(s):

Megan O. McDonald ◽

Nawaid Usmani ◽

Aldrich Ong ◽

Rashmi Koul ◽

Arbind Dubey ◽

...

Keyword(s):

Prostate Cancer ◽

Randomized Controlled Trial ◽

Controlled Trial ◽

Pelvic Radiotherapy ◽

Multicentre Phase ◽

Randomized Controlled ◽

High Risk Prostate Cancer ◽

Genitourinary Toxicity ◽

Risk Prostate Cancer ◽

Double Blinded

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Dose-Response in Radiotherapy for Localized Prostate Cancer: Results of the Dutch Multicenter Randomized Phase III Trial Comparing 68 Gy of Radiotherapy With 78 Gy

Journal of Clinical Oncology ◽

10.1200/jco.2005.05.2530 ◽

2006 ◽

Vol 24 (13) ◽

pp. 1990-1996 ◽

Cited By ~ 688

Author(s):

Stephanie T.H. Peeters ◽

Wilma D. Heemsbergen ◽

Peter C.M. Koper ◽

Wim L.J. van Putten ◽

Annerie Slot ◽

...

Keyword(s):

Prostate Cancer ◽

Randomized Trial ◽

Cancer Patients ◽

Radiation Therapy Oncology Group ◽

Three Dimensional ◽

Conformal Radiotherapy ◽

Phase Iii ◽

Clinical Failure ◽

Multicenter Randomized Trial ◽

Genitourinary Toxicity

Purpose To determine whether a dose of 78 Gy improves outcome compared with a conventional dose of 68 Gy for prostate cancer patients treated with three-dimensional conformal radiotherapy. Patients and Methods Between June 1997 and February 2003, stage T1b-4 prostate cancer patients were enrolled onto a multicenter randomized trial comparing 68 Gy with 78 Gy. Patients were stratified by institution, age, (neo)adjuvant hormonal therapy (HT), and treatment group. Four treatment groups (with specific radiation volumes) were defined based on the probability of seminal vesicle involvement. The primary end point was freedom from failure (FFF). Failure was defined as clinical failure or biochemical failure, according to the American Society of Therapeutic Radiation Oncology definition. Other end points were freedom from clinical failure (FFCF), overall survival (OS), and toxicity. Results Median follow-up time was 51 months. Of the 669 enrolled patients, 664 were included in the analysis. HT was prescribed for 143 patients. FFF was significantly better in the 78-Gy arm compared with the 68-Gy arm (5-year FFF rate, 64% v 54%, respectively), with an adjusted hazard ratio of 0.74 (P = .02). No significant differences in FFCF or OS were seen between the treatment arms. There was no difference in late genitourinary toxicity of Radiation Therapy Oncology Group and European Organisation for Research and Treatment of Cancer grade 2 or more and a slightly higher nonsignificant incidence of late gastrointestinal toxicity of grade 2 or more. Conclusion This multicenter randomized trial shows a significantly improved FFF in prostate cancer patients treated with a higher dose of radiotherapy.

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