A meta-analysis of two randomised trials of early chemotherapy in asymptomatic metastatic colorectal cancer

This report constitutes a prospectively planned meta-analysis combining two almost identical trials undertaken in Australasia and Canada to study the effect of starting chemotherapy immediately in asymptomatic patients with metastatic colorectal cancer. Patients (n=168) were randomised to receive either immediate or delayed treatment (at onset of predefined symptoms). Australasian patients received either weekly 5-fluorouracil and leucovorin (500 and 20 mg m−2, respectively) (n=59) or the daily × 5 Mayo Clinic schedule (425 and 20 mg m−2, respectively) (n=42). Canadian patients were treated with the Mayo schedule (n=67). Otherwise, the two studies were almost identical in design and each used the European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 instrument for measuring quality of life (QoL). Treatment was continued until 6 months had elapsed or disease progression occurred. Low accrual led to trial suspension before the predetermined sample size for either study was reached. Median survival was not significantly better with immediate treatment (median 13.0 vs 11.0 months; hazard ratio, 1.15; 95% confidence interval (CI) 0.79–1.72; P=0.49). There was no statistically significant difference in progression-free survival (time from randomisation until first evidence of progression after chemotherapy, 10.2 vs 10.8 months; hazard ratio, 1.08; 95% CI 0.71–1.64; P=0.73). There was no difference in overall QoL or its individual domains between the two treatment strategies at baseline or at any subsequent time point. Early treatment of asymptomatic patients with metastatic colorectal cancer did not provide a survival benefit or improved QoL compared to withholding treatment until symptoms occurred

Randomised, non-comparative phase II study of weekly docetaxel with cisplatin and 5-fluorouracil or with capecitabine in oesophagogastric cancer: the AGITG ATTAX trial

BACKGROUND: Docetaxel administered 3-weekly with cisplatin and 5-fluorouracil leads to better survival than does standard therapy in patients with oesophagogastric cancer, but leads to high rates of haematological toxicity. Weekly docetaxel is associated with less haematological toxicity. This randomised phase II study tested weekly docetaxel-based combination chemotherapy regimens, with the aim of maintaining their activity while reducing toxicity. METHODS: Patients with histologically confirmed metastatic oesophageal or gastric carcinoma were randomised to receive weekly docetaxel (30 mg m(-2)) on days 1 and 8, cisplatin (60 mg m(-2)) on day 1, and 5-fluorouracil (200 mg m(-2) per day) continuously, every 3 weeks (weekly TCF, wTCF); or docetaxel (30 mg m(-2)) on days 1 and 8 and capecitabine (1600 mg m(-2) per day) on days 1-14, every 3 weeks (weekly TX, wTX). RESULTS: A total of 106 patients were enrolled (wTCF, n=50; wTX, n=56). Response rates, the primary end point, were 47% with wTCF and 26% with wTX. Rates of febrile neutropenia were low in each arm. Median progression-free and overall survival times were 5.9 and 11.2 months for wTCF and 4.6 and 10.1 months for wTX, respectively. CONCLUSION: Weekly TCF and TX have encouraging activity and less haematological toxicity than TCF administered 3-weekly. Weekly docetaxel-based combination regimens warrant further evaluation in this disease

Thymidine Phosphorylase/β-tubulin III expressions predict the response in Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel

<p>Abstract</p> <p>Background</p> <p>To assess the role of Thymidine Phosphorylase and β-tubulin III in clinical outcome of Chinese advanced gastric cancer patients receiving first-line capecitabine plus paclitaxel.</p> <p>Methods</p> <p>The clinical data and tumor biopsies prior treatment from 33 advanced gastric cancer patients receiving capecitabine plus paclitaxel (cohort 1, experimental group) and 18 patients receiving capecitabine plus cisplatin (cohort 2, control group) in Beijing Cancer Hospital from July 2003 to December 2008 were retrospectively collected and analyzed for Thymidine Phosphorylase and β-tubulin III expressions by immunohistochemistry. The relationships between expressions of biomarkers and response or survival were determined by statistical analysis.</p> <p>Results</p> <p>The median age of 51 patients was 57 years (range, 27-75) with male 34 and female 17, and the response rate, median progression-free survival and overall survival were 43.1%, 120d and 265d. Among cohort 1, the response rate, median progression-free survival and overall survival in β-tubulin III positive (n = 22) and negative patients (n = 11) were 36.4%/72.7% (positive vs negative, <it>P </it>= 0.049), 86d/237d (<it>P </it>= 0.046) and 201d/388d (<it>P </it>= 0.029), respectively; the response rate (87.5% vs 14.3%, <it>P </it>= 0.01) and median progression-free survival (251d vs 84d, <it>P </it>= 0.003) in Thymidine Phosphorylase positive & β-tubulin III negative patients (n = 8) were also significantly higher than those in Thymidine Phosphorylase negative & β-tubulin III positive patients (n = 7). There was no correlation between β-tubulin III expression and response or survival among cohort 2 (n = 18).</p> <p>Conclusions</p> <p>In Chinese advanced gastric cancer, Thymidine Phosphorylase positive & β-tubulin III negative might predict response and prognosis to capecitabine plus paclitaxel chemotherapy. Further prospective evaluation in large samples should be performed to confirm these preliminary findings.</p

Temporal trends in treatment-related incidence of diseases of the circulatory system among Hodgkin lymphoma patients.

While Hodgkin lymphoma (HL) survival has improved, treatment-related complications remain a concern. As a measure of treatment-related diseases of the circulatory system (DCS) we report excess incidence of DCS and absolute risks among HL patients diagnosed in the modern treatment era. From the Swedish Cancer Register, we identified all HL patients diagnosed 1985 through 2013, at ages 18-80 years. Excess incidence rate ratios (EIRRs) with 95% confidence intervals (CIs) comparing excess DCS incidence between calendar periods were estimated overall, and at 5 and 10 years after diagnosis using flexible parametric models. Model-based predictions were used to obtain probabilities of being diagnosed with DCS, in the presence of competing risks. During follow-up, 726 (16%) of the 4,479 HL patients experienced DCS. Overall, the excess DCS incidence was lower during all calendar periods compared to the first (2009-2013 vs. 1985-1988: EIRR = 0.63, 95% CI: 0.42-0.95). The 5- and 10-year excess incidence of DCS decreased between 1985 and 1994 for 25-year-olds (5-year-EIRR1994  = 0.32, 95% CI: 0.12-0.92) and 60-year-olds (5-year-EIRR1994  = 0.45, 95% CI: 0.24-0.88), but remained stable thereafter. No improvements were observed among 75-year-olds. The probability of excess DCS remained the same throughout the study period. In 2009, the percentage of patients aged 25, 60 and 75 experiencing excess DCS within 5 years was 3.4, 15.0 and 17.0% (males) and 2.3, 10.8 and 12.6% (females). Treatment-related incidence of DCS has declined since the mid-1980s, but more recent improvements are absent and an excess risk remains. Continued efforts towards less toxic treatments are warranted, alongside primary prevention strategies