Case report: Efficacy and safety of regorafenib plus fluorouracil combination therapy in the treatment of refractory metastatic colorectal cancer.

Background: More than half of patients with colorectal cancer (CRC) present with metastatic disease or develop recurrent disease on first-line and second-line options. Treatment beyond the second line remains an area of unmet need for patients with progressive or recurrent disease. Methods: We retrospectively reviewed data of adult (>18 years old) patients with mCRC who received regorafenib + 5FU combination therapy at Houston Methodist Hospital with outcomes of interest including response rate, discontinuation due to side effects, and overall survival. Results: Seven patients received regorafenib + 5FU combination therapy for mCRC after receiving at least two other lines of therapy (including at least one fluorouracil-based therapy). Four patients (57%) achieved disease control in 7-12 weeks after therapy initiation while three patients developed recurrent disease. In patients who achieved disease control, no new adverse events were reported among patients with this combination. Conclusion: Regorafenib and Fluorouracil combination could be considered an option beyond the second line for patients with treatment-refractory metastatic colorectal cancer. Further studies, including a prospective trial, are needed to investigate the efficacy and safety of regorafenib plus 5FU therapy compared to other limited available therapies.

Cancer Disparities and Black American Representation in Clinical Trials Leading to the Approval of Oral Chemotherapy Drugs in the United States Between 2009 and 2019.

PURPOSE: Over the past 10 years, oral chemotherapy made up about half (45.6%) of all US Food and Drug Administration (FDA)-approved oncolytic and hematologic medications. Given the disparity in incidence and mortality rate because of certain cancers among Black Americans (BAs) in the United States, a review of BA's representation in the clinical trials that lead to the development and FDA approval of oral chemotherapy drugs becomes imperative. The objective of this study was to evaluate the reporting of race and inclusion of BA in clinical trials that led to the approval of oral chemotherapy medications by the FDA from 2009 to 2019 in the United States. Additionally, we evaluated the inclusion of BAs in clinical trials of three cancer types with the highest disparity rates among BAs (lung, breast, and prostate). METHODS: A retrospective review of all FDA-approved oral chemotherapy drug from 2009-2019 was obtained using the FDA's Hematology/Oncology Approvals & Safety Notifications website. Reports of racial and demographics inclusion were obtained from the clinical trials registry. RESULTS: Primary outcome: 142 clinical trials led to FDA approval of 81 oral chemotherapy agents between 2009 and 2019, among which 74 (52%) reported on at least one race and were included in our analysis. 35,933 participants were enrolled in these 74 clinical trials, among which 25,684 (71.47%), 6,061 (16.87%), 889 (2.47%), and 826 (2.30%) were White, Asian, Black, and Hispanic, respectively. BAs were also under-represented in the clinical trials of three cancer types with the highest disparity rates among this population. CONCLUSION: BAs were under-represented in clinical trials leading to FDA approval of oral chemotherapy drugs. There should be more BAs in cancer clinical trials to increase the generalizability of the results, improve outcomes, and eventually close the health disparity gap among this patient population.

Development and implementation of an electrolyte replacement protocol in the outpatient oncology infusion centers of a large academic healthcare system.

BACKGROUND: Patients receiving chemotherapy frequently experience electrolyte imbalances. Electrolyte replacement is, therefore, a necessity as patients may experience life-threatening symptoms.Study objective: The objective of this study was to evaluate the occurrence of low serum potassium and magnesium, and identify the rate of replacement for patients with low serum potassium and magnesium levels. Based on our findings, we developed and implemented a nursing-driven electrolyte replacement protocol. METHODS: Preimplementation phase - A retrospective review for serum potassium and magnesium values obtained during infusion clinic visit between 1 August and 31 October 2016 was conducted. Implementation phase - A nursing-driven electrolyte replacement protocol with medication order "smart-set" and order selection intelligence within EPIC Beacon was developed and implemented in May 2017. Postimplementation phase - The postimplementation phase data were collected from 1 August to 30 November 2017 using a similar approach as the preimplementation phase. RESULTS: Preimplementation phase - During the preimplementation phase of the study, a total of 1495 serum potassium levels and 1193 serum magnesium levels were obtained. Among the 152 patients who needed potassium replacement, 34% (n = 52) were replaced and among the 118 serum magnesium levels that needed replacement, 30% (n = 35) were replaced. Postimplementation phase - 3979 serum potassium and 2707 magnesium levels were obtained. Among the 170 patients who needed potassium replacement, 75% (n = 127) were replaced. Among the 142 patients who needed magnesium replacement, 73% (n = 104) were replaced. CONCLUSION: A 121% increase in potassium replacement and a 143% increase in magnesium replacement were identified after implementing this protocol.

Incidence of chemotherapy-induced peripheral neuropathy within 12 weeks of starting neurotoxic chemotherapy for multiple myeloma or lymphoma: a prospective, single-center, observational study.

PURPOSE: Chemotherapy-induced peripheral neuropathy (CIPN) may necessitate chemotherapy dose reduction, delay, or discontinuation. This pilot study tested feasibility of patient enrollment, CIPN screening, and data collection in cancer patients for a future clinical study that will assess the safety and efficacy of an intervention that may prevent CIPN. METHODS: This prospective, observational, single-center, pilot study included adults with newly diagnosed lymphoma or multiple myeloma receiving neurotoxic chemotherapy. Patients were enrolled between September 2016 and February 2017. The Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-Ntx) questionnaire was completed by patients at 3 time points: baseline, week 6, and week 12. The primary outcome was change in the neurotoxicity score between these time points. RESULTS: Of 33 patients approached for consent, 28 (85%) provided consent and were enrolled. The FACT/GOG-Ntx questionnaire was completed by 28 (100%) at baseline, 25 (89%) at week 6, and 24 (86%) at week 12. Average (standard deviation) neurotoxicity scores were 36.5 (6.6) at baseline, 34.0 (8.3) at week 6, and 30.6 (7.6) at week 12. Neurotoxicity scores changed from baseline by - 2.7 points (95% CI - 5.5 to 0.1; p = 0.061) at week 6 and - 6.0 points (95% CI - 5.6 to - 0.8; p = 0.012) at week 12. Clinically meaningful declines (decrease of > 10% from baseline) in neurotoxicity score were detected in 36% (9 of 25) at week 6 and in 67% (16 of 24) at week 12. CONCLUSION: Sixty-seven percent of patients experienced clinically significant CIPN within 12 weeks of starting chemotherapy. Feasibility metrics for enrollment, consent, CIPN assessment, and follow-up were met.

Evaluation of the prescribing patterns, adverse effects, and drug interactions of oral chemotherapy agents in an outpatient cancer center.

PURPOSE: Although oral chemotherapy offers advantages over intravenous chemotherapy, it creates a unique set of challenges. Potential barriers include treatment complexity, patient responsibility for medication adherence and monitoring, reduced healthcare contact, and increased financial burden. The purpose of this study is to estimate the prevalence of drug-related problems among a sample of patients treated with oral chemotherapy agents. METHODS: A single-center, retrospective chart review was conducted on patients prescribed oral chemotherapy at our institution between 1 January 2017 and 31 August 2017. The primary endpoint was the incidence of drug-related toxicities within 90 days of starting treatment. Secondary endpoints included incidence of drug-drug interactions, proportion of patients receiving medication education by a clinical pharmacist, and quantification of issues related to medication access. RESULTS: Charts of 100 patients were reviewed. Median time to oral chemotherapy receipt by the patient from the day the order was written was eight days. Prior to initiating therapy, 27% of patients received education by a clinical pharmacist. Toxicity checks were conducted by the provider at 30, 60, and 90 days for 80%, 65%, and 48% of patients, respectively. Treatment-related toxicities secondary to oral chemotherapy were reported by 79% of patients, with 55% classified as severe. Potential drug interactions were in 55% of the patients. CONCLUSION: Data from this study have highlighted avenues for pharmacists to make an impact on patients newly started on oral chemotherapy. Opportunities exist to increase patient education, ensure appropriate follow-up, and assess adherence while preventing and managing treatment-related toxicities.

Successful treatment of a stage IIIC small-cell carcinoma of the ovary hypercalcemic subtype using multi-modality therapeutic approach.

Small-cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is a rare but highly undifferentiated, aggressive malignancy that primarily affects young women. Due to its early onset, unclear familial history and vague presenting symptoms, most SCCOHT patients present late with advanced disease. The prognosis is extremely poor, with <10% disease-free survival for advanced stages. Although several therapeutic regimens have been proposed, to date there is no consensus on the optimal strategy. Here, we describe a successful case of advanced-stage SCCOHT of the left ovary treated with cytoreductive surgery, semi-intense chemotherapy, high-dose consolidative chemotherapy, autologous hematopoietic stem cell transplantation and pelvic radiation with long-term survival. Given the almost universal mortality of advanced SCCOHT in long-term follow-up, we believe this case highlights the importance of prompt diagnosis when a young patient presents with abdominal swelling and hypercalcemia as well as early, aggressive, combined modality treatment. This case is also especially remarkable given the patient underwent fertility preservation surgery, which is not recommended by most of the current literature. However, as therapies improve and more young patients may survive SCCOHT, the question of fertility will increase in relevance. We believe the pros and cons of conservation should be discussed in detail with the patient.