Rare complications of multikinase inhibitor treatment

ABSTRACT Objective: The advent of multikinase inhibitor (MKI) therapy has led to a radical change in the treatment of patients with advanced thyroid carcinoma. The aim of this manuscript is to communicate rare adverse events that occurred in less than 5% of patients in clinical trials in a subset of patients treated in our hospital. Subjects and methods: Out of 760 patients with thyroid cancer followed up with in our Division of Endocrinology, 29 (3.8%) received treatment with MKIs. The median age at diagnosis of these patients was 53 years (range 20-70), and 75.9% of them were women. Sorafenib was prescribed as first-line treatment to 23 patients with differentiated thyroid cancer and as second-line treatment to one patient with advanced medullary thyroid cancer (MTC). Vandetanib was indicated as first-line treatment in 6 patients with MTC and lenvatinib as second-line treatment in two patients with progressive disease under sorafenib treatment. Results: During the follow-up of treatment (mean 13.7 ± 7 months, median 12 months, range 6-32), 5/29 (17.2%) patients presented rare adverse events. These rare adverse effects were: heart failure, thrombocytopenia, and squamous cell carcinoma during sorafenib therapy and squamous cell carcinoma and oophoritis with intestinal perforation during vandetanib treatment. Conclusions: About 3 to 5 years after the approval of MKI therapy, we learned that MKIs usually lead to adverse effects in the majority of patients. Although most of them are manageable, we still need to be aware of potentially serious and rare or unreported adverse effects that can be life-threatening.

Bevacizumab toxicity in heavily pretreated recurrent epithelial ovarian, fallopian tube, and primary peritoneal cancers / 부인종양

OBJECTIVE: Bevacizumab was recently approved by the US Food and Drug Administration for use in recurrent platinum resistant epithelial ovarian cancer (EOC), fallopian tube cancer (FTC), or primary peritoneal cancer (PPC) when no more than two prior cytotoxic regimens have been used; due to concerns for gastrointestinal perforation. We sought to determine bevacizumab-related toxicities in heavily pretreated recurrent EOC. METHODS: We performed a retrospective chart review of patients with recurrent EOC, FTC, and PPC from 2001 to 2011. Patients who received at least two prior chemotherapy regimens before bevacizumab were included. Medical records were reviewed for bevacizumab associated toxicities. The Wilcoxon-Mann-Whitney test was used to compare quantitative variables. Survival was estimated with the Kaplan-Meier method. RESULTS: Sixty patients met inclusion criteria. At the start of bevacizumab treatment, the median age was 60 years and the median body mass index was 26.5 kg/m². More than 50% of patients received bevacizumab after three prior cytotoxic regimens. Grade 3 or higher bevacizumab associated toxicity events occurred in four patients, including one patient who developed a rectovaginal fistula. The median overall survival from the start of bevacizumab treatment was 21.05 months (95% CI, 18.23 to 32.67; range, 1.9 to 110 months). The number of cytotoxic regimens prior to bevacizumab treatment did not differ in those that experienced a toxicity versus those that did not (p=0.66). CONCLUSION: The use of bevacizumab in heavily pretreated EOC, FTC, or PPC is worth consideration.

Hypermagnesemia Accompanied with Colonic Perforation in a Hemodialysis Patient

We report a case of a chronic hemodialysis patient who developed hypermagnesemia due to an overdose of magnesium-containing laxative and paralytic ileus resulting in colonic perforation. Despite intravenous calcium infusion and daily hemodialysis, the patient developed ischemic colitis and intestinal perforation. Colonic perforation accompanied with hypermagnesemia in hemodialysis patients has rarely been reported. This case suggests that hypermagnesemia should be considered in renal failure patients as this can result in life-threatening events despite prompt treatment.

A Rare Case of Free Bowel Perforation Associated with Infliximab Treatment for Stricturing Crohn's Disease / 대한소화기학회지

Crohn's disease is characterized by chronic transmural inflammation of the bowel and is associated with serious complications, such as bowel strictures, abscesses, fistula formation, and perforation. As neither medical nor surgical therapy provides a cure for Crohn's disease, the primary goals of therapy are to induce and maintain remission and prevent complications. As a biologic agent, infliximab, a monoclonal antibody to tumor necrosis factor, is indicated for refractory luminal and fistulizing Crohn's disease that does not respond to other medical therapies or surgery. Infliximab has proven to be very effective for inducing and maintaining remission in Crohn's disease; however, infliximab treatment has several potential complications. Here, we report a case of free perforation following a therapeutic response after an initial dose of infliximab for Crohn's disease. This is the first case report describing a free perforation in a Crohn's disease patient after an initial dose of infliximab.

Bowel Perforation after Erlotinib Treatment in a Patient with Non-Small Cell Lung Cancer

Erlotinib is accepted as a standard second-line chemotherapeutic agent in patients with non-small cell lung cancer who are refractory or resistant to first-line platinum-based chemotherapy. There has been no previous report of bowel perforation with or without gastrointestinal metastases related to erlotinib in patients with non-small cell lung cancer. The exact mechanism of bowel perforation in patients who received erlotinib remains unclear. In this report, we report the first case of enterocutaneous fistula in a female patient with metastatic non-small cell lung cancer 9 months, following medication with erlotinib as second-line chemotherapy.

Indomethacin-induced colon perforation in Bartter's syndrome.

Bartter's syndrome (BS) is an inherited renal tubular disorder characterized by hypokalemia, hypochloremic metabolic alkalosis, and hyperaldosteronism with normal blood pressure. A 22-year-old woman was referred at 23 week of gestation. Polyhydramnios was detected and the chloride level of the amniotic fluid was high. The mother was treated with indomethacin from 26 to 31 week of gestation. The newborn was delivered at 34 week of gestation. At 8th day of life, indomethacin was also started for the baby. After three days, a colonic perforation developed. Indomethacin-induced colon perforation is uncommon in antenatal Bartter's syndrome. This patient indicates that administration of indomethacin in both antenatal and/or early postnatal period may be associated with colonic perforation.

Perforación primaria del colon asociada a ingesta de esteroides: presentación de un caso / Primary colonic perforation related to steroids intake

Se presenta un paciente masculino de 64 años de edad, con historia de dolor abdominal de 15 horas de evolución, quien refiere un cuadro inespecífico inicialmente, para luego convertirse en un abdomen agudo quirúrgico con peritonitis, sin historia de fiebre y sin elevación de glóbulos blancos. Antecedente de tener diagnóstico de Mieloma Múltiple y recibiendo tratamiento con dexametasona por 14 meses. Se documenta por laparotomía exploradora perforación única de colon sigmoides y peritonitis difusa, sin evidencia de lesión diverticular subyacente ni causa infecciosa o isquémica en el colon perforado. Se maneja con resección de colon sigmoides y colostomía con bolsa de Hartmann. Ante la falta de evidencia de otra causa aparente, esta perforación se atribuye al uso prolongado de esteroides y se analiza el caso con respecto a la literatura disponible hasta el momento

Neutropenic enterocolitis and cecal perforation in acute lymphatic leukemia.

A ten year old boy who died of the consequences of an infrequent gastrointestinal complication, whilst on induction chemotherapy for acute lymphatic leukemia, is being reported. Recent trends in the diagnosis and management of typhilitis or neutropenic enterocolitis have been reviewed.