Association between adjuvant docetaxel-based chemotherapy and breast cancer-related lymphedema.

Docetaxel-based chemotherapy can lead to fluid retention and secondary peripheral edema of the extremities, but its association with lymphedema remains unclear. In this study, we retrospectively investigated the relationship between adjuvant docetaxel-based chemotherapy and breast cancer-related lymphedema. Patients with stage II/III breast cancer who received adjuvant chemotherapy were evaluated for lymphedema on the basis of arm circumference measurements. The incidence and risk factors of lymphedema were determined by Kaplan-Meier and Cox proportional hazard analyses. A total of 320 patients were included. Specifically, 182 patients received docetaxel and 138 patients did not receive docetaxel. Compared with docetaxel-free chemotherapy, docetaxel-based chemotherapy significantly increased the 2.5-year cumulative incidence of all-grade lymphedema (19.91 vs. 32.09%; P=0.011), which was further verified in grade 1-2 (P=0.012), but not in grade 3 lymphedema (P=0.448). Similar results were found in a comparison between docetaxel and nontaxane, but not in a comparison between docetaxel and other taxanes. Multivariate analysis showed that docetaxel-based chemotherapy is an independent risk factor for both all-grade (hazard ratio=1.73; P=0.017) and grade 1-2 lymphedema (hazard ratio=1.87; P=0.022). In conclusion, adjuvant docetaxel-based chemotherapy significantly increased the risk of breast cancer-related lymphedema.

Polymorphisms in mismatch repair genes are associated with risk and microsatellite instability of gastric cancer, and interact with life exposures.

BACKGROUND: Epigenetic alterations of DNA mismatch repair (MMR) genes are associated with risk of gastric cancer (GC) by causing microsatellite instability (MSI). Less understood is the association of common polymorphisms in MMR genes with the risk and MSI phenotype of GC. METHODS: A hospital-based study was conducted in China with 423 cases and 454 matched controls. Four potentially functional polymorphisms were selected and analyzed: rs1800734 in MLH1, rs2303428 in MSH2, rs735943 in EXO1, and rs11797 in TREX1. RESULTS: The rs1800734 G-allele was associated with decreased risk of GC (GA or GG vs AA, OR=0.72; 95% CI: 0.50-1.05; Ptrend=0.029). For combined effects, a dose-response manner was observed in which GC risk was increased with increasing number of at-risk genotypes (Ptrend=0.039); this manner mainly existed in MSI GC (Ptrend=0.047) rather than in microsatellite stability GC, though neither single polymorphism was linked with MSI. For exposures, modified effects were observed from green tea drinking and soy foods intake on rs11797 (P for interaction=0.007 and 0.016, respectively). CONCLUSIONS: The MLH1 rs1800734 polymorphism is associated with GC risk. Those at-risk genotypes have a joint effect on GC risk, which contributes to the MSI phenotype of GC. Life exposures modify GC risk, stratified by MMR genotypes.

Thalidomide Combined with Chemotherapy in Treating Patients with Advanced Colorectal Cancer.

OBJECTIVE: To assess the safety and effectiveness of thalidomide (produced by CHANGZHOU PHARMACEUTICAL FACTORY CO.LTD) combined with chemotherapy in treating patients with advanced colorectal cancer. METHOD: A consecutive cohort of pretreated patients with advanced colorectal cancer were treated with thalidomide combined with chemotherapy. And chemotherapy for patients with advanced colorectal cancer were administered according to the condition of patients. Thalidomide was orally administered at a dosage of 50mg/day to 150 mg/day before sleeping for at least 14 days. After at least 14 days of treatment, safety and side effects were evaluated. RESULTS: There were 12 female and 3 male patients with advanced cancer recruited into this study, including 9 patients with colon, 6 patients with rectal cancer. The median age of patients was 57(41- 82) years. Partial response was observed in 2 patients (2/15), and stable disease in 3 patients(3/15). Incidences of Grade 1 to 2 myelosuppression was observed in 1/15 patients, and Grade 1 to 2 elevation of hepatic enzyme was recorded in 1/15 patients. Adverse effects on the gastrointestinal tract were documented in 1/15 patients, and were Grade 1. No Grade 3-4 toxicities were diagnosed. No treatment related death was found. CONCLUSIONS: Thalidomide combined with chemotherapy was safe and mildly effective in treating patients with advanced colorectal cancer. However, further study should be conducted to clarify the effectiveness of this combination.

Surrogate end points for survival in the target treatment of advanced non-small-cell lung cancer with gefitinib or erlotinib.

BACKGROUND: It is controversial for the use of survival surrogate end points including response rate (RR), disease control rate (DCR), time to progression, and progression-free survival (PFS) in trials of molecular targeted agents. Our aim was to determine the correlations of these surrogates with survival in the treatment of advanced non-small-cell lung cancer (ANSCLC) with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib. METHODS: Summary data of median survival time (MST) and surrogates from prospective trials of EGFR-TKIs in ANSCLC were identified. Patient- or trial-related characteristics were introduced as covariates. Simple and multivariate linear regression models were fitted for MST and each surrogate, respectively. And the significance of each surrogate as a survival marker was compared by calculating the area under their receiver operating characteristic (ROC) curves. RESULTS: Sixty eligible trials (9,903 patients) were enrolled. RR, DCR, and PFS were all strongly associated with MST. In their simple linear regression models, the coefficient of determination (R(2)) was 0.83 (p < 0.000001), 0.58 (p < 0.0001), and 0.70 (p < 0.0001), respectively. And in their multivariate linear regression models, the standard coefficient was 0.71 (p < 0.001), 0.40 (p < 0.001), and 0.74 (p < 0.001), respectively, while RR and PFS were the preferred survival predictors in the ROC analysis. CONCLUSION: RR or PFS may serve as an appropriate survival surrogate in the clinical trials of EGFR-TKIs for ANSCLC.