Phase II study of S-1 on alternate days plus bevacizumab in patients aged ≥ 75 years with metastatic colorectal cancer (J-SAVER)
BackgroundAlternate-day administration of S-1 is thought to reduce toxicities. This phase II study evaluated S-1 on alternate days combined with bevacizumab as first-line treatment for elderly patients with metastatic colorectal cancer.Patients and methodsEligible patients had histologically proven colorectal adenocarcinoma, measurable metastatic lesions, age ≥ 75 years, Eastern Cooperative Oncology Group performance status ≤ 1, no previous chemotherapy, and refused oxaliplatin- or irinotecan-containing regimens. Patients received 40 mg, 50 mg, or 60 mg (body surface area ≤ 1.25 m2, > 1.25 to ≤ 1.50 m2, or > 1.50 m2, respectively) of S-1 twice orally on Sunday, Monday, Wednesday, and Friday every week. Bevacizumab (7.5 mg/kg) was administered every 3 weeks. The primary endpoint was progression-free survival.ResultsOf 54 enrolled patients, 50 patients were evaluated for efficacy and 53 for safety. The median age was 79 years (range 75–88 years). The median progression-free survival was 8.1 months (95% confidence interval (CI) 6.7–9.5 months). The median overall survival was 23.1 months (95% CI 17.4–28.8 months). The response rate was 44% (95% CI 30.2–57.8%), and the disease control rate was 88% (95% CI 79.0–97.0%). Grade 3 or higher hematologic, non-hematologic, and bevacizumab-related adverse events occurred in 9%, 11%, and 25% of patients, respectively. The most common grade 3 and 4 treatment-related adverse events were hypertension (11%), nausea (6%), fatigue (6%), anemia (6%), and proteinuria (6%). Only 6 patients discontinued treatment due to adverse events.ConclusionS-1 on alternate days combined with bevacizumab showed better tolerability and comparable survival compared with the results of similar studies.
Bevacizumab is equally effective and no more toxic in elderly patients with advanced colorectal cancer: a subgroup analysis from the AGITG MAX trial: an international randomised controlled trial of Capecitabine, Bevacizumab and Mitomycin C.
BACKGROUND
In an ageing population, a greater proportion of geriatric patients will be considered for systemic chemotherapy. Colorectal cancer (CRC) is a common malignancy and will be a major health issue in geriatrics. We used the MAX population to investigate whether age affected the improved outcome found in CRC when bevacizumab is added to capecitabine chemotherapy.


PATIENTS AND METHODS
MAX, a three arm study of Capecitabine (C) versus CBevacizumab (CB) versus CBMitomycin C (CBM), found an improvement in progression-free survival (PFS), with addition of B [+/- mitomycin C (MMC)] to C. This analysis assesses the effect of adding B (+/- MMC) to C on PFS, overall survival (OS), response rate (RR), toxicity and dose intensity in geriatric patients (age ≥ 75 years).


RESULTS
Ninety-nine patients (21%) were aged 75-86 years. Baseline characteristics were well balanced. Eighty-eight per cent commenced C at the lower optional dose of 2000 mg/m(2)/day; days 1-14, q21 (61% for <75 years) and 88% were Eastern Cooperative Oncology Group 0-1. Co-morbidities were as expected in this population. The addition of B significantly improved PFS in geriatric patients(C 5.8 months versus CB 8.8 months, Hazard ratio (HR) 0.65 and C versus CBM 10.4 months HR 0.38). The interaction test for OS, RR and PFS revealed no impact of age. Dose intensity was maintained >90% in all patients. There were no major differences in toxicity patterns between age cohorts.


CONCLUSIONS
Addition of B to C significantly improved PFS in this geriatric population, with similar benefits to those aged <75 years. Treatment was well tolerated with no signal of increased toxicity (including thromboembolism) when compared with those aged <75 years.
Matching the Implant to the Breast: A Systematic Review of Implant Size Selection Systems for Breast Augmentation
Background: For primary breast augmentation, several implant selection systems have been described to guide the surgeon with choosing from a variety of manufactured implant dimensions and properties. Controversy exists regarding the most efficacious method of selecting an appropriate implant size that best matches the patient’s breast. Methods: The goal of this systematic review was to provide a comprehensive list of documented implant size selection systems, and to critically evaluate them. Implant size selection systems were grouped into categories based on selection principles. Articles were evaluated based on reported outcome measures and methodologic quality. Results: Thirty-three implant size selection systems were included in the final analysis. Only 12 percent of articles (four of 33) reported clinical outcomes that could be compared to accepted literature values or industry standards. Articles that described tissue-based planning systems, which use clinical guidelines to determine the optimal patient-specific implant dimensions, were of highest methodologic quality using the Methodological Index for Non-Randomised Studies scale, when compared to systems that used breast “dimensional” analyses that stress tissues to the desire of the patient and/or surgeon, and compared to systems that did not use breast measurement (means ± SD, 6.0 ± 1.4, 1.4 ± 2.3, and 0.0 ± 0.0, respectively). Conclusions: There is some evidence to support tissue-based planning as a superior approach to implant size selection planning; studies that used tissue-based planning reported lower reoperation rates compared with industry standards and accepted literature values. The authors offer several suggestions on how to improve the methodologic quality of future studies describing new implant selection systems.