Chemotherapy delivery for resected colorectal cancer liver metastases: Management and outcomes in routine clinical practice.

BACKGROUND: International guidelines recommend peri-operative chemotherapy for patients with resectable colorectal cancer liver metastases (CRCLM). Chemotherapy delivery in routine practice is not well described. METHODS: All cases of CRC who underwent resection of LM in 2002-2009 were identified using the population-based Ontario Cancer Registry. Electronic treatment records identified chemotherapy delivered within 16 weeks before or after hepatectomy. All pathology reports were reviewed to describe extent of LM. Modified Poisson regression was used to evaluate factors associated with chemotherapy delivery. Cox proportional hazards model and propensity score analysis were used to explore the association between post-operative chemotherapy and cancer-specific (CSS) and overall (OS) survival. RESULTS: We identified 1310 patients. Sixty-two percent of cases (815/1310) received peri-operative chemotherapy; 25% (200/815) pre-operative, 45% (366/815) post-operative, and 31% (249/815) pre- and post-operative. Utilization of chemotherapy increased over time from 51% in 2002 (57/112) to 73% in 2009 (157/216, p < 0.001). Fifty-four percent of patients received FOLFOX, 41% FOLFIRI, and 10% 5-FU monotherapy. Factors that were independently associated with greater utilization of post-operative chemotherapy included younger age (p < 0.001), female sex (p = 0.050), shorter disease-free interval (p = 0.006), and no prior adjuvant chemotherapy (p < 0.001). Utilization of chemotherapy varied substantially across geographic regions (from 24% to 71%, p = 0.001). Post-operative chemotherapy was associated with improved CSS (HR 0.58, 95%CI 0.44-0.76) and OS (HR 0.49, 95%CI 0.38-0.61); results were consistent in propensity score analysis. CONCLUSION: Utilization of chemotherapy for resected CRCLM in routine practice has evolved with emerging evidence. Post-operative chemotherapy is associated with improved survival in the general population.

Factors associated with referral to medical oncology and subsequent use of adjuvant chemotherapy for non-small-cell lung cancer: a population-based study.

BACKGROUND: Adjuvant chemotherapy (act) for non-small-cell lung cancer (nsclc) is associated with improved survival in the general population, but may be underutilized. We explored the factors associated with referral to medical oncology and subsequent use of act among all patients with resected nsclc in Ontario, Canada. METHODS: The Ontario Cancer Registry was used to identify all incident cases of nsclc diagnosed in Ontario during 2004-2006. We linked electronic records of treatment and of physician billing to identify surgery, act, and medical oncology consultation. A multivariate logistic regression model was used to evaluate factors associated with referral to medical oncology and subsequent use of act. RESULTS: Among 3354 cases of nsclc resected in Ontario during 2004-2006, 1830 (55%) were seen postoperatively by medical oncology, and 1032 (31%) were treated with act. Patients more than 70 years of age were less likely than younger patients to have a consultation [odds ratio (or): 0.4; p < 0.001]. A higher proportion of cases with stage ii or iii nsclc than with stage i disease were referred (ors: 2.7, 2.0 respectively; p < 0.005). We observed substantial geographic variation in the proportion of surgical cases referred (range: 32%-88%) that was not explained by differences in case mix. Among cases referred to medical oncology, older patients (age 60-69 years, or: 0.4; age 70+ years, or: 0.1; p < 0.001) with greater comorbidity (Charlson comorbidity index: 3+; or: 0.5; p < 0.05) and a longer postoperative stay (median length of stay: 7+ days; or: 0.7; p = 0.001) were less likely to receive act. Use of act was greater in patients with stage ii or iii than with stage i disease (ors: 3.0, 2.7 respectively; p < 0.001); use also varied with geographic location (range: 46%-63%). CONCLUSIONS: The initial decision to refer to medical oncology is associated with age and stage of disease, and those factors have an even greater effect on the decision to offer act. Comorbidity and postoperative length of stay were not associated with initial referral, but were associated with use of act in patients seen by medical oncology.

Effect of PSC 833, a potent inhibitor of P-glycoprotein, on the growth of astrocytoma cells in vitro.

Malignant astrocytomas have been found to express P-glycoprotein (Pgp, mdr1 gene product). It was hypothesized that in addition to conferring multidrug resistance, Pgp is intimately associated with the development of astrocytomas. Accordingly, we studied the effect of PSC 833 (PSC, Novartis), a potent inhibitor of Pgp, on the growth of Pgp-expressing astrocytoma cells. The results showed that in all the cell lines tested, PSC (10-60 microM) inhibited the growth as well as induced cell death. Cells exposed to PSC exhibited DNA ladder characteristic of apoptosis. PSC-induced cell death could be reversed by Z-VAD-fmk, a general caspase inhibitor, indicating that PSC-induced cell death was characteristic of caspase-mediated apoptosis. These results suggest a novel therapeutic strategy in the treatment of malignant astrocytomas by inhibitors of Pgp.