Early-Onset Colorectal Adenocarcinoma in the IDEA Database: Treatment Adherence, Toxicities, and Outcomes With 3 and 6 Months of Adjuvant Fluoropyrimidine and Oxaliplatin.

PURPOSE: Early-onset (EO) colorectal cancer (CRC, age < 50 years) incidence is increasing. Decisions on optimal adjuvant therapy should consider treatment adherence, adverse events, and expected outcomes in a population with life expectancy longer than later-onset (LO) CRC (age ≥ 50 years). MATERIALS AND METHODS: Individual patient data from six trials in the International Duration Evaluation of Adjuvant Chemotherapy database were analyzed. Characteristics, treatment adherence, and adverse events in stage II or III EO-CRC and LO-CRC were compared. To reduce confounders of non-cancer-related deaths because of age or comorbidities, time to recurrence (3-year relapse-free rate) and cancer-specific survival (5-year cancer-specific mortality rate) were considered. RESULTS: Out of 16,349 patients, 1,564 (9.6%) had EO-CRC. Compared with LO-CRC, EO-CRC had better performance status (86% v 80%, P < .01), similar T stage (% T1-3/T4: 76/24 v 77/23, P = .97), higher N2 disease rate (24% v 22%, P < .01), more likely to complete the planned treatment duration (83.2% v 78.2%, P < .01), and received a higher treatment dose intensity, especially with 6-month regimens. Gastrointestinal toxicity was more common in EO-CRC; hematologic toxicity was more frequent in LO-CRC. Compared with LO-CRC, significantly worse cancer-specific outcomes were demonstrated especially in high-risk stage III EO-CRC: lower 3-year relapse-free rate (54% v 65%; hazard ratio [HR] 1.33; 95% CI, 1.14 to 1.55; P value < .001) and higher 5-year cancer-specific mortality rate (24% v 20%; HR 1.21; 95% CI, 1.00 to 1.47; P value < .06). In this subgroup, no difference was observed with 3 or 6 months of therapy, with equally poor disease-free survival rates (57% v 56%; HR 0.97; 95% CI, 0.73 to 1.29; P value = .85). CONCLUSION: Young age is negatively prognostic in high-risk stage III CRC and associated with significantly higher relapse rate; this is despite better treatment adherence and higher administered treatment intensity, suggesting more aggressive disease biology.

Bisphosphonates in the adjuvant setting of breast cancer therapy--effect on survival: a systematic review and meta-analysis.

BACKGROUND: The role of bisphosphonates (BP) in early breast cancer (BC) has been considered controversial. We performed a meta-analysis of all randomized controlled trials (RCTs) that appraised the effects of BP on survival in early BC. METHODS: RCTs were identified by searching the Cochrane Library, MEDLINE databases and conference proceedings. Hazard ratios (HRs) of overall survival (OS), disease-free survival (DFS) and relative risks of adverse events were estimated and pooled. RESULTS: Thirteen trials met the inclusion criteria, evaluating a total of 15,762 patients. Meta-analysis of ten trials which reported OS revealed no statistically significant benefit in OS for BP (HR 0.89, 95% CI = 0.79 to 1.01). Meta-analysis of nine trials which reported the DFS revealed no benefit in DFS (HR 0.95 (0.81-1.12)). Meta-analysis upon menopausal status showed a statistically significant better DFS in the BP-treated patients (HR 0.81(0.69-0.95)). In meta-regression, chemotherapy was negatively associated with HR of survival. CONCLUSIONS: Our meta-analysis indicates a positive effect for adjuvant BP on survival only in postmenopausal patients. Meta-regression demonstrated a negative association between chemotherapy use BP effect on survival. Further large scale RCTs are warranted to unravel the specific subgroups that would benefit from the addition of BP in the adjuvant setting.

Doxorubicin-induced ovarian toxicity.

BACKGROUND: Young cancer patients may occasionally face infertility and premature gonadal failure. Apart from its direct effect on follicles and oocytes, chemotherapy may induce ovarian toxicity via an impact on the entire ovary. The role of doxorubicin in potential ovarian failure remains obscure. Our intention was to elucidate doxorubicin-related toxicity within ovaries. METHODS: Female mice were injected intraperitoneally with 7.5 or 10 mg/kg doxorubicin and their ovaries were visualized in vivo by high resolution MRI, one day and one month following treatment. Ovaries of other treated mice were excised and weighed at the same post-treatment intervals. Ovarian histological sections were stained for TUNEL or active caspase-3 and follicles were counted and categorized. Ovulation rates were evaluated in superovulated female mice treated with doxorubicin. RESULTS: A single injection of doxorubicin resulted in a major reduction in both ovarian size and weight that lasted even one month post treatment. A dramatic reduction in ovulation rate was observed one week after treatment, followed by a partial recovery at one month. Histological examination revealed positive staining of TUNEL and active caspase-3. We observed a significant reduction in the population of secondary and primordial follicles one month following treatment. CONCLUSIONS: Our results may imply a mechanism of chemotherapy-induced ovarian toxicity, manifested by reduced ovulation and accompanied by a reduction in ovarian size, caused probably by an acute insult to the ovary.