4-(4-Hy-droxy-phenyl)-2,2,4-trimethyl-7,8-benzo-thia-chroman, a fused-ring counterpart of thia-Dianin's compound.

The title compound, C22H22OS [systematic name: 4-(1,3,3-trimethyl-2,3-di-hydro-1H-4-thia-phenanthren-1-yl)phenol], crystallizes unsolvated from nitro-methane as colourless prisms (m.p. 425-427 K) in the polar monoclinic space group Ia with Z' = 2 (mol-ecules A and B). Both independent mol-ecules possess a very similar proximal conformation, this referring to the juxtaposition of the 4-hy-droxy-phenyl substituent with respect to the syn-related methyl group. In the crystal, mol-ecule A is linked to mol-ecule B by an O-H⋯O hydrogen bond. In turn, mol-ecule B exhibits a weak O-H⋯π inter-action with the phenolic group of mol-ecule A related by a-glide symmetry. Together, these lead to [100] chains.

Survival Impact of Adjuvant Chemotherapy for Resected Locally Advanced Rectal Adenocarcinoma.

BACKGROUND: Recent data has created uncertainty regarding the benefit of adjuvant fluoropyrimidine-containing chemotherapy following preoperative chemoradiotherapy and surgical resection for locally advanced rectal cancer (LARC). In particular, patients with a pathologic complete response (pCR) may derive no benefit from adjuvant chemotherapy. PATIENTS AND METHODS: This is a retrospective analysis of patients with LARC, diagnosed between January 1, 2003 and December 31, 2014 at 3 Melbourne health services. Patients were identified from the Australian Comprehensive Cancer Outcomes and Research Database, where a defined data set is prospectively collected on consecutive patients. Patient demographics, pCR rates, postoperative treatment, recurrence, and survival were analyzed. RESULTS: A total of 717 patients with LARC were identified, of whom 555 (77%) had received preoperative long-course chemoradiation followed by surgery. Four hundred fifty-two of 555 patients (81%) subsequently received adjuvant fluoropyrimidine-based chemotherapy. At a median follow-up of 45.9 months, 95 (21%) patients in the adjuvant chemotherapy group and 20 (19%) in the surveillance group had relapsed. Five-year relapse-free survival was 77% in the adjuvant chemotherapy group and 71% in the surveillance group with no significant difference on univariate analysis (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.58-1.51; P = .780). No significant impact on relapse-free survival was seen for either pCR or non-pCR patients. Five-year overall survival (OS) was 85% in the adjuvant chemotherapy group and 74% in the surveillance group with a nonsignificant trend towards OS benefit (HR, 0.62; 95% CI, 0.37-1.05; P = .074). A significant OS benefit favoring adjuvant chemotherapy was seen in the non-pCR subset of patients (HR, 0.49; 95% CI, 0.28-0.86; P = .014). CONCLUSION: A high proportion of patients in this routine practice cohort received adjuvant chemotherapy following preoperative treatment and surgery for LARC. Adjuvant chemotherapy administration was associated with a significant improvement in 5-year OS only in the patients with a non-pCR.

Time course of safety and efficacy of aflibercept in combination with FOLFIRI in patients with metastatic colorectal cancer who progressed on previous oxaliplatin-based therapy.

BACKGROUND: Patients with metastatic colorectal cancer (mCRC) previously-treated with oxaliplatin benefit significantly from the addition of aflibercept to FOLFIRI in relation to overall survival, progression-free survival and response rate. PATIENTS AND METHODS: The results for efficacy and safety over the time course of the VEGF Trap (aflibercept) with irinotecan in colorectal cancer after failure of oxaliplatin regimen trial were analysed based on data from 1226 patients randomised to receive FOLFIRI plus either aflibercept (n=612) or placebo (n=614). Hazard ratios (HR) by 6-month time period were estimated using a piecewise Cox proportional hazard model. Severity of adverse events (AEs) was graded using National Cancer Institute Common Terminology Criteria, version 3.0. RESULTS: The estimated probabilities of survival were 38.5% versus 30.9% at 18 months, 28.0% versus 18.7% at 24 months and 22.3% versus 12.0% at 30 months, for the aflibercept- and placebo-treated arms, respectively. The proportional improvement in the HR over time was consistent with the survival probability results; survival at 24 months was improved by 50% and almost doubled at 30 months. The majority of worst-grade AEs occurred within the first four cycles of treatment and in a small percent of treatment cycles and were mostly reversible. Common chemotherapy- and anti-vascular epithelial growth factor (VEGF)-associated AEs occurred rarely and in a small proportion of cycles with the majority being of single occurrence. CONCLUSIONS: The addition of aflibercept to FOLFIRI showed a continued and persistent improvement in overall survival over time in patients with mCRC. Although grade 3-4 AEs were more frequent in the aflibercept arm, they occurred in early treatment cycles and decreased sharply following initial presentation.

Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial.

PURPOSE: The antiangiogenic agent aflibercept (ziv-aflibercept in the United States) in combination with 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) significantly improved survival in a phase III study of patients with metastatic colorectal cancer (mCRC) previously treated with an oxaliplatin-based regimen. In the present analysis, outcomes were evaluated in prespecified subgroups to assess the consistency of the treatment effect. METHODS: Patients were randomised to receive FOLFIRI plus aflibercept or placebo every 2weeks until disease progression or unacceptable toxicity occurred. Efficacy and safety outcomes were analysed with respect to demographic and baseline characteristics, and stratification factors (prior bevacizumab treatment and Eastern Cooperative Oncology Group performance status). RESULTS: Median overall survival (OS, months [95.34% confidence interval (CI)]) for aflibercept versus placebo was 12.5 (10.8-15.5) versus 11.7 (9.8-13.8) in patients with prior bevacizumab treatment and 13.9 (12.7-15.6) versus 12.4 (11.2-13.5) in patients with no prior bevacizumab treatment. The p value for interaction was 0.5668, indicating there was no heterogeneity in these subgroups. For OS and progression-free survival (PFS), there was a significantly greater benefit (at the 2-sided 10% level) of treatment for patients with liver only metastases versus patients with no liver metastases/liver metastases with other organ involvement (p value for interaction: 0.0899 [OS]; 0.0076 [PFS]). There was no evidence of heterogeneity in treatment effect in any of the other subgroups examined. CONCLUSIONS: The benefits of aflibercept in combination with FOLFIRI in patients with mCRC previously treated with oxaliplatin were maintained across the specified patient subgroups, including in patients with or without prior bevacizumab treatment.