The Influence of Adjuvant Chemotherapy Dose Intensity on Five-Year Outcomes in Resected Colon Cancer: A Single Centre Retrospective Analysis

There is evidence that achieving a dose intensity > 80% in adjuvant colon cancer treatment improves survival. In total, 192 consecutive patients with resected stage III and high-risk stage II colon cancer that received adjuvant chemotherapy were retrospectively analyzed. Patients who received at least 6 weeks of adjuvant therapy were included. The primary objective was to assess the influence of dose index (DI) and relative dose intensity (RDI) on DFS and OS at 3 and 5 years in patients receiving fluorouracil-based doublet therapy with oxaliplatin (FOLFOX)(5-FU and oxaliplatin assessed separately), or capecitabine monotherapy. In the capecitabine group, DFS rates for 3 and 5 years were 66.7% and 57.6%, respectively, while OS rates were 80.3% and 66.7%, respectively. Those who received FOLFOX had DFS rates of 76.9% and 71.2% at 3 and 5 years, respectively. OS rates were 86.4% and 76.7% at 3 and 5 years, respectively. Median RDI was 73.8% for capecitabine and 76.3% and 85.6% for the oxaliplatin and 5-FU components respectively. Based on a multivariate analysis in patients receiving FOLFOX, those with an oxaliplatin DI > 80% had improvements in DFS and OS compared to those with an oxaliplatin DI of ≤ 80%. Otherwise, there was no significant difference in DFS or OS when comparing patients who achieved an RDI or a DI of above versus below 80% in the patients receiving adjuvant chemotherapy for resected colon cancer.

Comparison of standard versus reduced-dose pegfilgrastim on clinical outcomes and chemotherapy dose intensity in patients with advanced pancreatic cancer receiving cytotoxic combination chemotherapy (NAPPCG) in an outpatient oncology infusion clinic.

e15710 Background: Pegfilgrastim use has been shown to reduce the incidence of febrile neutropenia when given at recommended dosage (6 mg) following myelosuppressive chemotherapy. Despite lack of supportive data, many prescribers have adopted the practice of utilizing reduced dosages (3-4 mg) of pegfilgrastim, often citing bone pain as reason for dose reduction. We sought to explore the impact of reduced-dose pegfilgrastim on chemotherapy dose intensity in patients with pancreatic cancer treated with the triplet combination of nab-paclitaxel, cisplatin and gemcitabine (NabPlagem) at our facility. Methods: A retrospective analysis was conducted on all patients who received NabPlagem chemotherapy in combination with pegfilgrastim during the period of 1/1/16 - 9/30/16. Patients who received at least 2 cycles were considered evaluable. Chemotherapy was administered on Days 1 and 8 of a 21-day cycle with pegfilgrastim administered Days 2 and 9. Chemotherapy doses were considered full-intensity if no reduction made from original treatment schema (i.e. 125 mg/m2 nab-paclitaxel, 25 mg/m2 cisplatin and gemcitabine 1000 mg/m2) with no doses delayed or omitted from treatment plan. Results: A total of 54 chemotherapy cycles were administered, with patients receiving between 5-13 cycles. Of these 54 cycles, 14 were given with reduced-dose pegfilgrastim (26%) and 40 at full dosage (74%). In the patients receiving full dose pegfilgrastim, treatment delays and omissions were observed in 5% cycles (n = 2), with no dose reductions required. Full dose-intensity was obtained in 90% cycles (36/40). In comparison, treatment delays and omissions were observed in 14% cycles given with reduced-dose pegfilgrastim. Dose reductions were required in 10/14 cycles (71%). Full dose-intensity was observed in 28.5% cycles (4/14). Conclusions: Based on this data, dosage of pegfilgrastim dose is an important factor in maintaining dose-intensity of chemotherapy, and full dosing (6 mg) should be preferred dosing schedule when used with myelosuppressive chemotherapy.

Outcomes of solid tumor malignancies in patients of Jehovah’s Witness faith.

e18176 Background: Jehovah's Witness (JW) patients with cancer present unique challenges due to their refusal of blood and blood products which limits supportive care options in the setting of cancer treatment. This study was aimed at determining their cancer specific outcomes. Methods: A retrospective analysis of case records of JW with solid tumors presented between 2005 and 2015 was conducted. Patient demographic data, diagnosis, treatment details and survival outcomes were collected and analysed. Results: A total of 63 JW were identified (39 females; 24 males); median age was 70 years (25-90). The most common cancer was breast (n=16) followed by colorectal (n=10). 27 JW had advanced disease (TNM stage 4), 48 patients had ECOG 0-1 and 22 JW had anaemia (Hb<120g/L for women and <130g/L for men) at the time of diagnosis. While surgery and radiation were uniformly accepted when recommended, 7 out of 42 refused chemotherapy. Median OS was 64 months in early stage (TNM stages 1-3) and 11 months in advanced stage. At presentation blood transfusion was considered unacceptable by all patients under any circumstances. 19 patients rejected transfusion even after symptomatic or life threatening anaemia. They had 1 year overall survival rate of 42% compared with 84% for those who did not require transfusion (HR 4.31, CI 1.96- 9.49, P=0.001). When adjusted for age and ECOG, these results were significant in early stage (P <0.026) but not in late stage (P= 0.6). Treatment was suboptimal in 14 JW patients due to early treatment discontinuation or inferior chemotherapy regimen used to avoid pancytopenia. Median OS in this group was 15 months compared to 46 months who had optimal treatment (HR 2.5, CI 1.07- 6.27, P =0.034). 17 JW received bone marrow stimulating agents like erythropoietin or G-CSF. They helped with dyspnoea and maintaining chemotherapy dose intensity. Conclusions: Refusal of blood components may have negative impact on long term cancer outcome of JW due to compromised chemotherapy dose intensity. Strategies to deliver optimum therapy while being sensitive of religious perceptions will help in improving outcomes for this group.

Effect of single agent high-dose methotrexate-related acute kidney injury on length of hospitalization and relative dose intensity in adult patients with central nervous system lymphoma

Purpose Grade ≥3 adverse effects prolong hospitalization and reduce chemotherapy dose intensity. The purpose of this study was to evaluate the rate and severity of high-dose methotrexate-related acute kidney injury and analyze its effect on hospital length of stay and relative chemotherapy dose intensity. Methods This was a retrospective cohort analysis. Patients receiving ≥1 dose of high-dose methotrexate were analyzed for acute kidney injury and length of stay. Patients receiving ≥6 cycles of induction therapy were included in the analysis of relative chemotherapy dose intensity. Chi squared analysis was used to determine the differences between dichotomous data; Student’s t-test for parametric data and Mann-Whitney U test for non-parametric data for continuous variables. Statistical analyses were performed with IBM SPSS Statistics (version 21). Results Twenty-six patients and 194 treatment encounters were identified. Thirteen patients were evaluated for relative chemotherapy dose intensity. Grade ≥3 acute kidney injury occurred in four patients (15% of patients; 2% of encounters). There were no grade 5 adverse events. Mean length of stay for encounters with grade ≥3 acute kidney injury was almost three times longer than for those with ≤ grade 2 acute kidney injury (p = 0.041). Mean relative chemotherapy dose intensity was reduced approximately in half for patients experiencing grade ≥3 acute kidney injury (p < 0.01). The most common adverse events were hypokalemia and nausea. Proton pump inhibitors were the most frequently co-administered medications with the potential to affect high-dose methotrexate pharmacokinetics. Conclusion At our cancer program, the rate of grade ≥3 acute kidney injury with high-dose methotrexate is similar to that reported by others. Grade ≥3 acute kidney injury following high-dose methotrexate administration significantly prolonged length of stay and reduced relative chemotherapy dose intensity.