Sixty-nine patients with disseminated testicular cancer and no prior retroperitoneal lymphadenectomy treated with cisplatin, vinblastine, and bleomycin with or without doxorubicin were evaluated for semen analysis, serum gonadotropins, and testosterone. Since 1979, 41 men have been prospectively studied. Before treatment 77% were oligospermic, 17% were azoospermic, and only 6.6% could meet requirements for sperm banking. After 2 mo of therapy, 96% were azoospermic. A group of 28 patients treated between 1975 and 1979 were retrospectively evaluated. Normal sperm counts were found in 46% of those studied. Only 17% were azoospermic. Thirty-two percent have impregnated their wives, resulting in 5 healthy babies, 1 spontaneous abortion, and 3 ongoing pregnancies. These results show that (1) significant impairment of spermatogenesis exists before therapy, precluding the possibility of sperm banking in most patients, (2) combination chemotherapy in testicular cancer has substantial effects on gonadal function, rendering almost all patients azoospermic, and (3) a high degree of recovery of spermatogenesis occurs sometime after 2-3 yr from the initiation of treatment.

e15744 Background: FOLFIRINOX (FFN) and Gemcitabine plus nab-paclitaxel (GN) have been established as first line chemotherapy in advanced pancreatic cancer (PC). But there is no head-to-head randomized trial data available to support preferable first line choice between these two regimens. Methods: We retrospectively evaluated 154 chemotherapy-naïve locally advanced and metastatic PC patients treated with FFN or GN at KU Cancer Center between January 2011 and November 2016. FFN consisted of Oxaliplatin 85mg/m2, Irinotecan 180mg/m2, 5-FU 400mg/m2 as a bolus and 2,400 mg/m2over 46 hour on days 1 and 15 every 4 weeks. GN consisted of Gemcitabine 1000mg/m2 plus nab-paclitaxel 125mg/m2 day1,8,15 every 4 weeks. We compared characteristics, efficacy and adverse events between FFN and GN. Results: 107 patients were treated with FFN and 47 patients with GN as first line therapy. Demographic and baseline characteristics (FFN/GN) were as follows: Median age 61/63 years, ECOG performance status (0-1): 90% / 83%, Gender (male): 57% / 54%, distant metastases: 52%/70%, biliary stenting: 41%/20%, locally advanced tumor: 48%/30%, pancreatic head tumors: 63%/55%, median number of cycles: 4/4 respectively. Objective response rate (13% vs. 10%), Stable disease rate (76% vs 82%) and disease control rate (89% vs. 92%, p = 0.5) were similar in FFN and in GN. Median PFS was 11.7 months (95% CI: 7.2-16.1) in FFN and 5.7 months (95% CI: 2.7-8.8) in GN [p = 0.07]. Median OS was 15.9 months (95% CI: 13.7-18.1) in FFN and 10.8 months (95% CI: 7.1 – 14.5) in GN [p = 0.17]. Incidences of grade 3 or higher adverse effects were neutropenia (33% vs. 17%), anemia (14% vs 31%), thrombocytopenia (28% vs 6%), elevated creatinine (2.8% vs 4%), elevated transminases (3.7% vs 6%), diarrhea (5% vs. 0%), and peripheral neuropathy (6% vs. 6%) respectively. Conclusions: Patients treated with FFN showed statistically better PFS compared to GN. However this difference in PFS did not translate into statistically significant difference in OS. Response rates were similar. Incidences of adverse events were relatively more with FFN compared to GN as expected.

Importance Recent changes in guidelines for managing Clostridioides difficile infections (CDI) have placed fidaxomicin as a first-line treatment. Objective To estimate the net cost of first-line fidaxomicin compared to vancomycin in the American and Canadian healthcare systems and to estimate the price points at which fidaxomicin would become cost saving for the prevention of recurrence. Data sources and study selection We identified randomized, placebo-controlled trials directly comparing fidaxomicin with vancomycin that reported on recurrence. Medication costs were obtained from the Veterans Affairs Federal Supply Schedule (US) and the Quebec drug formulary (Canada). The average cost of a CDI recurrence was established through a systematic review for each country. Data extraction, synthesis and outcome measures For efficacy, data on CDI recurrence at day 40 were pooled using a restricted maximal likelihood random effects model. For the cost review, the mean cost across identified studies was adjusted to reflect May 2022 dollars. These were used to estimate the net cost per recurrence prevented with fidaxomicin and the price point below which fidaxomicin would be cost saving. Results The estimated mean system costs of a CDI recurrence were $15 147USD and $8806CAD, respectively. Preventing one recurrence by using first-line fidaxomicin over vancomycin would cost $38 222USD (95%CI $30 577–$57 332) and $13 760CAD (95%CI $11 008–$20 640), respectively. The probability that fidaxomicin was cost saving exceeded 95% if priced below $1140USD or $860CAD, respectively. Conclusions and Relevance An increased drug expenditure on fidaxomicin may not be offset through recurrence prevention unless the fidaxomicin price is negotiated.

ImportanceRecent changes in the Infectious Diseases and Healthcare Epidemiology Societies of America (IDSA-SHEA) guidelines for managing Clostridioides difficile infections (CDI) have placed fidaxomicin as first-line treatment for CDI.ObjectiveTo estimate the net cost of first line fidaxomicin as compared to vancomycin in the American and Canadian healthcare systems and to estimate the price points at which fidaxomicin would become cost saving.Data sourcesWe identified all randomized controlled trials comparing fidaxomicin with vancomycin through the 2021 IDSA-SHEA guideline update. Medication costs were obtained from wholesale prices (US) and the Quebec drug formulary (Canada). The average cost of a CDI recurrence was established through two systematic reviews using PubMed.Study selectionFor fidaxomicin efficacy, we included double-blind and placebo-controlled trials. For the systematic review of recurrence costs, studies were included if they were primary research articles, had a cost-analysis of CDI, included cases of recurrent CDI, and were calculated with cost parameters from American or Canadian healthcare systems. Studies were excluded if the population was solely pediatric or hospitalized.Data extraction and SynthesisFor the efficacy meta-analysis, data was pooled using a random effects model. For the costs review, literature screening was performed by 2 independent reviewers. The mean cost across identified studies was adjusted to 2021 dollars.Main Outcomes and MeasuresThe primary outcome of the meta-analysis was CDI recurrence at day 40. The primary outcome of the systematic review was the average cost of a CDI recurrence in the American and Canadian healthcare systems. The objective was to estimate the net cost per recurrence prevented and the price point below which fidaxomicin would be cost saving.ResultsAt current drug pricing, the estimated additional cost of a 10-day course of fidaxomicin compared to vancomycin in order to prevent one recurrence was $46,178USD (95%CI $36,942-$69,267) and $13,760CAD (95%CI $11,008-$20,640), respectively. The estimated mean systemic cost of a CDI recurrence was $14,506USD and $8,588CAD, respectively. When priced below $1550USD and $800CAD, fidaxomicin was likely to become cost saving.Conclusions and RelevanceThe increased drug expenditure on fidaxomicin will not be offset through recurrence prevention unless fidaxomicin price is re-negotiated.Key PointsQuestionAt what price point does new guideline recommendations for changing from vancomycin to fidaxomicin for first line C. difficile infection (CDI) therapy become cost saving?FindingsFor a 10-day course, we estimated that compared to vancomycin, treatment with fidaxomicin costs an additional $46,178USD to prevent one CDI recurrence and that treating one recurrence costs $14,506USD. The current cost of fidaxomicin is only partially offset through prevention of recurrences. Upfront therapy with fidaxomicin would be cost saving if the price were reduced below $1550USD per treatment.MeaningNew guideline updates could add billions in additional drug costs for CDI treatment.

received DMT. Patients with DMT were less likely to have a corticosteroid claim than patients not receiving DMT (39% vs 62%), and less likely to have an ER visit (39% vs 54%) or hospitalization episode (18% vs 29%).