Gemcitabine and Taxane Adjuvant Therapy with Chemoradiation in Resected Pancreatic Cancer: A Novel Strategy for Improved Survival?

BACKGROUND: Gemcitabine-taxane combination chemotherapy has demonstrated a survival benefit clinically in metastatic pancreatic cancer (PC). The authors present their experience with gemcitabine and docetaxel (gem/tax)-based adjuvant treatment (Rx) after surgery with curative intent. METHODS: Patients with de novo resectable PC from January 2010 to December 2015 were identified from the authors' institutional database and registry. The study included only patients who received gem/tax as their initial Rx administered exclusively at the authors' institution with or without chemoradiation (CRTx). Survival analysis was performed using Kaplan-Meier methods, and prognostic factors were investigated by Cox proportional hazard modeling. RESULTS: Of 102 patients identified, 58 met the study criteria. The median age at diagnosis was 65 years, with 55% of the patients undergoing an R1 resection (margin ≤ 1 mm). Tumor characteristics included a median tumor size of 28 mm, a poor differentiation rate of 54%, and a lymph node positivity of 67%. Most of the patients (90%, 52/58) completed 80% or more of the 24 week Rx. Of these patients, 71% received post-gem/tax CRTx Rx. Grade 3 or 4 toxicity was observed in 52% of the patients. The median follow-up period was 51.2 months, and the observed median overall survival (OS) was 52 months [95% confidence interval (CI) 27.4-not reached]. The actuarial 5-year OS was 49% (95% CI 33.7-63.4%). In the multivariate analysis, an R1 resection and American Joint Committee on Cancer (AJCC) stage 2 versus stage 1 disease were negatively associated with OS, whereas administration of CRTx was positively associated with OS. CONCLUSIONS: Adjuvant gem/tax with or without CRTx is feasible, with a favorable OS. Future prospective studies of gem/taxane-based adjuvant Rx for PC are warranted.

Adjuvant radiation therapy, androgen deprivation, and docetaxel for high-risk prostate cancer postprostatectomy: Results of NRG Oncology/RTOG study 0621.

BACKGROUND: Phase 3 trials have demonstrated a benefit from adjuvant radiation therapy (ART) for men who have adverse factors at radical prostatectomy (RP). However, some patients have a high risk of progression despite ART. The role of systemic therapy with ART in this high-risk group remains to be defined. METHODS: Patients who had either a post-RP prostate-specific antigen (PSA) nadir > 0.2 ng/mL and a Gleason score ≥7 or a PSA nadir ≤0.2 ng/mL, a Gleason score ≥8, and a pathologic tumor (pT) classification ≥ pT3 received 6 months of androgen-deprivation therapy (ADT) plus radiotherapy and 6 cycles of docetaxel. The primary objective was to assess whether the addition of ADT and docetaxel to ART resulted in a freedom from progression (FFP) rate ≥ 70% compared with an expected rate of 50%. Multivariate logistic and Cox regression analyses were used to model associations between factors and outcomes. RESULTS: In total, 74 patients were enrolled. The median follow-up was 4.4 years. The pathologic tumor classification was pT2 in 4% of patients, pT3 in 95%, and pT4 in 1%. The Gleason score was 7 in 18% of patients and ≥8 in 82%. Post-RP PSA levels were ≤0.2 ng/mL in 53% of patients and >0.2 ng/mL in 47%. The 3-year FFP rate was 73% (95% confidence interval, 61%-83%), and the 3-year cumulative incidence of biochemical, distant, and local failure was 26%, 7%, and 0%, respectively. In multivariate models, postprostatectomy PSA nadir was associated with 3-year FFP, Gleason score, and PSA with biochemical failure. Grade 3 and 4 neutropenia was common; however, only 3 episodes of febrile neutropenia occurred. Late toxicities were not impacted by the addition of systemic therapy. CONCLUSIONS: Combined ADT, docetaxel, and ART for men with high-risk prostate cancer after prostatectomy exceeded the prespecified study endpoint of 70% 3-year FFP. Phase 3 trials assessing combined local and systemic therapies for these high-risk patients are warranted. Cancer 2017;123:2489-96. © 2017 American Cancer Society.

A prospective analysis of health-related quality of life in intermediate and high-risk prostate cancer patients managed with intensity modulated radiation therapy, with vs. without hormonal therapy.

INTRODUCTION: Combined radiotherapy and hormonal treatment are recommended for intermediate- and high-risk prostate cancer (CaP). This study compared the long-term effects on health-related quality of life (HRQoL) of intermediate- and high-risk CaP patients managed with radiation therapy (RT) with vs. without hormone therapy (HT). METHODS: Patients with intermediate- and high-risk CaP enrolled in the Center for Prostate Disease Research diagnosed from 2007 to 2017 were included. EPIC and SF-36 questionnaires were completed and HRQoL scores were compared for patients receiving RT vs. RT + HT at baseline (pretreatment), 6, 12, 24, 36, 48, and 60 months after CaP diagnosis. Longitudinal patterns of change in HRQoL were modeled using linear regression models, adjusting for baseline HRQoL, age at CaP diagnosis, race, comorbidities, National Comprehensive Cancer Network (NCCN) risk stratum, time to treatment, and follow-up time. RESULTS: Of 164 patients, 93 (56.7%) received RT alone and 71 (43.3%) received RT + HT. Both groups reported comparable baseline HRQoL. Patients receiving RT+HT were more likely to be NCCN high risk as compared to those receiving only RT. The RT + HT patients experienced worse sexual function, hormonal function, and hormonal bother than those who only received RT; however, HRQoL recovered over time for the RT + HT group. No significant differences were observed between groups in urinary and bowel domains or SF-36 mental and physical scores. CONCLUSION: Combined RT + HT treatment was associated with temporary lower scores in sexual and hormonal HRQoL compared with RT only. Intermediate- and high-risk CaP patients should be counseled about the possible declines in HRQoL associated with HT.

Phase II study of long-term androgen suppression with bevacizumab and intensity-modulated radiation therapy (IMRT) in high-risk prostate cancer.

PURPOSE: We report a Phase II trial assessing the acute and late toxicities of intensity-modulated radiation therapy (IMRT), long-term androgen suppression (LTAS), and bevacizumab in patients with high-risk localized prostate cancer. METHODS AND MATERIALS: We treated 18 patients with LTAS with bicalutamide and goserelin in combination with bevacizumab and IMRT. Bevacizumab (10 mg/kg every 2 weeks) was administered for the first 16 weeks, and 15 mg/kg was then given every 3 weeks for 12 additional weeks, with an IMRT dose of 77.9 Gy to the prostate, 64.6 Gy to the seminal vesicles, and 57 Gy to the pelvic lymph nodes. Patients were eligible if they had clinical stage T2b to T4, a Gleason sum score of 8 to 10, or a prostate- specific antigen level of 20ng/mL or greater. The primary endpoint of the study was evaluation of acute and late toxicities. RESULTS: The median age was 69 years, with a median pretreatment prostate-specific antigen level of 12.5 ng/mL and Gleason score of 8. The pretreatment clinical stage was T1c in 4 patients, T2 in 11, and T3 in 3. All patients completed IMRT with median follow-up of 34 months (range, 28-40 months) The most common Grade 2 or higher toxicities were hypertension (61% of patients with Grade 2 and 11% with Grade 3), proteinuria (28% with Grade 2 and 6% with Grade 3), and leucopenia (28% with Grade 2). No Grade 4 or higher acute toxicities were reported. Late toxicities included proctitis (6% of patients with Grade 2 and 11% with Grade 3), rectal bleeding (6% with Grade 2 and 11% with Grade 3), hematuria (6% with Grade 2), proteinuria (17% with Grade 2), hyponatremia (6% with Grade 3), cystitis (6% with Grade 3), and urinary retention (6% with Grade 2 and 11% with Grade 3). Grade 4 prostatitis occurred in 1 patient (6%). CONCLUSIONS: Bevacizumab does not appear to exacerbate the acute effects of IMRT. Late toxicities may have been worsened with this regimen. Further investigations of bevacizumab with LTAS and IMRT should be performed cautiously.