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BACKGROUND: Fertility counseling is recommended for adolescent and young adult (AYA) women facing gonadotoxic cancer therapy. However, fertility care is subspecialized medical care offered at a limited number of institutions, making geographic access a potential barrier to guideline-concordant care. We assessed the relationship between geographic access and receipt of fertility counseling among AYA women with cancer. METHODS: Using data from the North Carolina Central Cancer Registry, we identified women diagnosed with lymphoma, gynecologic cancer, or breast cancer at ages 15-39 years during 2004-2015. Eligible women were invited to complete an online survey on various topics, including fertility counseling. Geographic access was measured, using geocoded addresses, as vehicular travel time from residence to the nearest fertility clinic available at diagnosis. Multivariable regression models were used to examine the association between travel time and receipt of fertility counseling by provider type: health care provider vs fertility specialist. RESULTS: Analyses included 380 women. Median travel time to a fertility clinic was 31 (IQR: 17-71) minutes. Overall, 75% received fertility counseling from a health care provider and 16% by a fertility specialist. Women who lived ≥30 minutes from a clinic were 13% less likely to receive fertility counseling by a health care provider (PR:0.87; 95% CI:0.75-1.00) and 49% less likely to receive counseling by a fertility specialist (PR:0.51; 95% CI:0.28-0.93). CONCLUSIONS: Women who lived further away from fertility clinics were less likely to receive fertility counseling. IMPACT: Interventions to improve access to fertility counseling should include strategies to alleviate the burden of geographic access.
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BACKGROUND: To describe reasons for deviations from planned chemotherapy treatments in women with nonmetastatic breast cancer that contribute to less-than-planned receipt of chemotherapy. METHODS: Electronic medical records for patients receiving chemotherapy were reviewed for adverse events and treatment modifications. Log-binomial regression models were used to estimate relative risks (RRs) with 95% CIs to examine associations between chemotherapy modifications, patient characteristics, and treatment modalities. RESULTS: Delays in chemotherapy initiation (7%) were for surgical complications (58%), personal reasons (16%), and other (26%; port malfunction, infections, and obtaining extra imaging). Delays during chemotherapy (38%) were for infections (20%), neutropenia (13%), and personal reasons (13%). Dose reductions (38%) were for neuropathy (36%), unknown causes (9%), anemia (9%), and neutropenia (8%). Early treatment discontinuations (23%) were for neuropathy (29%). Patients receiving paclitaxel/nab-paclitaxel (RR 2.05; 95% CI, 1.47-2.87) and an anthracycline (RR 1.89; 95% CI, 1.39-2.57) reported more dose delays during chemotherapy. Black race (RR 1.46; 95% CI, 1.07-2.00), stage 3 (RR 1.79; 95% CI, 1.09-2.93), and paclitaxel/nab-paclitaxel receipt (RR 1.39; 95% CI, 1.02-1.90) increased the likelihood of dose reduction. Both Black race (RR 2.06; 95% CI, 1.35-3.15) and receipt of paclitaxel/nab-paclitaxel (RR 1.93; 95% CI, 1.19-3.13) increased the likelihood of early discontinuation. Patients receiving anthracyclines had higher rates of hospitalizations during chemotherapy (RR: 1.79; 95% CI, 1.11-2.89). CONCLUSION: Toxicities are the most common reason for treatment modifications and need close monitoring in high-risk groups for timely intervention. Dose reductions and early treatment discontinuations occurred more for Black patients and need further study.
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BACKGROUND: FOLFIRI is a standard regimen for metastatic colorectal cancer (mCRC). We hypothesized that a pharmacogenomic-directed strategy where more efficient irinotecan metabolizers (UGT1A1 *1/*1 homozygotes and *1/*28 heterozygotes) receive higher-than-standard irinotecan doses would improve progression-free survival (PFS) compared to non-genotype selected historical controls with acceptable toxicity. METHODS: In this phase II multicenter study irinotecan dosing in first-line FOLFIRI and bevacizumab for mCRC was based on UGT1A1 genotype with *1/*1, *1/*28, and *28/*28 patients receiving 310 mg/m2, 260 mg/m2, and 180 mg/m2, respectively. Primary endpoint was PFS. Secondary endpoints were investigator and patient-reported adverse events, and estimation of overall survival (OS). RESULTS: One-hundred patients were enrolled with 91 evaluable for PFS and 83 evaluable for best response. Median PFS was 12.5 months (90% CI 10.9, 15.4), shorter than the anticipated alternative hypothesis of 14 months. PFS by genotype was 12.5 months (90% CI 10.9, 17.4) for *1/*1, 14.6 months (90% CI 11.8, 17.5) for *1/*28, and 6 months (90% CI 2.3, 7.7) for *28/28, respectively. OS was 24.5 months (90% CI 19.1, 30.7) and by genotype was 26.5 (90% CI 19.1, 32.9), 25.9 (90% CI 17.6, 37.7), and 13.4 (90% CI 2.3, 20.5) months for *1/*1, *1/*28, and *28/*28, respectively. G3/4 toxicity was similar between all subgroups, including diarrhea and neutropenia. CONCLUSIONS: A pharmacogenomic-directed irinotecan strategy improved PFS in the *1/*1 and *1/*28 genotypes with higher rates of neutropenia and similar rates of diarrhea compared to expected with standard FOLFIRI dosing. However, improvements in response rate and PFS were modest. This strategy should not change standard practice for mCRC patients in the first-line setting.