Final findings from the CONTROL trial: Strategies to reduce the incidence and severity of neratinib-associated diarrhea in patients with HER2-positive early-stage breast cancer.

BACKGROUND: Neratinib is an irreversible pan-HER tyrosine kinase inhibitor approved for HER2-positive early-stage and metastatic breast cancer. Diarrhea is the most frequent side effect and the most common reason for early discontinuation. The phase II CONTROL trial investigated antidiarrheal prophylaxis or neratinib dose escalation (DE) for prevention of diarrhea. We present complete study results including final data for two DE strategies. METHODS: Patients who completed trastuzumab-based adjuvant therapy received neratinib 240 mg/day for 1 year. Early cohorts investigated mandatory prophylaxis with loperamide, then additional budesonide or colestipol. Final cohorts assessed neratinib DE over the first 2 (DE1) or 4 weeks (DE2). The primary endpoint was incidence of grade ≥3 diarrhea. Health-related quality of life (HRQoL) was assessed using FACT-B and EQ-5D-5L. RESULTS: 563 patients were enrolled into six cohorts. All strategies reduced grade ≥3 diarrhea with the lowest incidence in DE1 (DE1 13%; colestipol + loperamide [CL] 21%, DE2 27%; budesonide + loperamide [BL] 28%; loperamide [L] 31%; colestipol + loperamide as needed [CL-PRN] 33%). Diarrhea-related discontinuations occurred early and were lowest in DE1 (DE1 3%; CL 4%; DE2 6%; CL-PRN 8%; BL 11%; L 20%). More patients stayed on neratinib for the prescribed period versus historical controls. Prior pertuzumab use did not affect rates of grade ≥3 diarrhea, diarrhea-related discontinuations, or treatment duration. Early transient reductions in HRQoL scores were observed. CONCLUSIONS: These complete results from CONTROL show improved neratinib tolerability with proactive management at the start of therapy. Two-week neratinib DE with loperamide as needed was particularly effective. GOV REGISTRATION NUMBER: NCT02400476.

A phase I and II trial of epirubicin, cisplatin, 24-hour infusion 5 fluorouracil and sodium folinate in patients with advanced esophagogastric carcinomas.

AIM: Advanced esophagogastric carcinoma has a poor prognosis. Palliative chemotherapy provides a survival advantage and improved quality of life. Epirubicin, cisplatin and continuous infusional 5-fluorouracil (5-FU) (ECF) is a well-established chemotherapy regimen but a continuous chemotherapy infusion is not always feasible or acceptable. METHODS: We conducted a phase I and II trial of a modified version of ECF, utilizing 5-FU as a 24-h infusion on day 1 and day 8 of a 21-day cycle, administered with sodium folinate as a modulator of 5-FU (ECSF). In the phase I study the dose of 5-FU was increased in successive cohorts from 1250 mg/m(2) , 1500 mg/m(2) , and 1750 mg/m(2) to 2000 mg/m(2) per 24 h. RESULTS: Dose limiting toxicity of febrile neutropenia was encountered at 2000 mg/m. The recommended dose for 5-FU was 1750 mg/m(2) . Overall 29 patients were treated with ECSF of whom 27 were evaluable for toxicity. The response rate was 45% on an intention-to-treat analysis with a complete response rate of 3%. The median response rate was 4.1 months and the median survival was 10.7 months. A total of 23 patients (72%) obtained clinical benefit with improvement in dysphagia or weight gain. central venous catheter (CVC) complications were observed in 12 (41%) patients. CONCLUSION: ECSF was associated with a response rate and survival similar to that reported with standard ECF. ECSF may provide an alternative regimen to standard ECF when a continuous ambulatory infusion pump is not feasible or not preferred by the patient. CVC complications are a limitation.

A Randomized Study of Electronic Diary versus Paper and Pencil Collection of Patient-Reported Outcomes in Patients with Non-Small Cell Lung Cancer.

BACKGROUND: Hand-held electronic devices may provide a simple reproducible means by which quality of life (QOL) may be documented in patients with cancer. However, the QOL scales that are routinely used were originally validated when used with paper and pencil data collection. Patient-reported outcomes acquired using hand-held electronic devices (electronic patient-reported outcomes [e-PRO]) may not be the same as those acquired using paper and pencil, so validation of this method of data collection is needed. OBJECTIVES: This study aimed to compare the results of e-PRO and paper and pencil collection of Functional Assessment of Cancer Therapy-Lung (FACT-L) and EuroQol-5 Dimension (EQ-5D) QOL data in patients with advanced non-small cell lung cancer (NSCLC), and to ascertain patients' preferences for the different modes of collection. METHODS: This randomized, single-cohort, crossover study was performed in a tertiary referral hospital cancer center. Fifty patients with previously treated locally advanced or metastatic NSCLC were randomized in a 1 : 1 ratio to complete either paper versions of the questionnaires (FACT-L and EQ-5D) followed by the e-PRO versions, or the e-PRO questionnaire followed by the paper versions. RESULTS: The majority (88%) of the FACT-L and all (100%) of the EQ-5D individual question responses were within ±1 point of each other when data collection via e-PRO and via pencil and paper were compared. There was no significant difference between the mean total FACT-L scores obtained using the two methods; however, 29% of patients had a difference between FACT-L total scores obtained with the two methods that was greater than ±6 points. The mean completion time was shorter for the paper and pencil method than the e-PRO method (p < 0.0001). However, most patients stated that they preferred the e-PRO method over paper and pencil (60% vs 12%). CONCLUSION: This study suggests that the mode of administration of the FACT-L and EQ-5D had a relatively small effect on the mean responses given to the questionnaires in patients with advanced NSCLC. However, at the individual patient level, data varied considerably between the different modes of administration. Therefore, the group results obtained using the e-PRO should be similar to the originally validated paper method, with the advantages of improved patient acceptability and ease of reliable interfacing with trial databases.

Erythema nodosum associated with diffuse, large B-cell non-Hodgkin lymphoma detected by FDG PET.

A patient is described with non-Hodgkin lymphoma and erythematous skin nodules suspected to be erythema nodosum. The patient underwent serial fluorodeoxyglucose (FDG) positron emission tomography (PET), which demonstrated normalization of FDG uptake by the lymphoma after 2 cycles of chemotherapy, but there was new abnormal uptake involving the subcutaneous tissues of the lower extremities. A typical skin lesion was sampled and showed the appearance of erythema nodosum with no evidence of lymphoma. The FDG uptake gradually diminished on serial PET imaging after treatment with nonsteroidal antiinflammatory drugs. In view of the recognized association of erythema nodosum with malignancy and the differential rate of response to chemotherapy, the lesions of erythema nodosum may be a source of a false-positive PET interpretation, and histologic assessment should be considered.