Phase I study of tamibarotene monotherapy in pediatric and young adult patients with recurrent/refractory solid tumors.

PURPOSE: Tamibarotene is a synthetic retinoid that inhibits proliferation and induces differentiation of malignant cells by binding to the retinoic acid receptor α/ß. Previous in vitro studies have shown that some pediatric solid tumors with retinoic acid receptors differentiate in response to retinoic acid. We conducted a phase I dose-escalation study to determine the recommended dose of tamibarotene for further study in pediatric and young adult patients with recurrent/refractory solid tumors. METHODS: Pediatric and young adult patients with recurrent/refractory solid tumors were administered tamibarotene at 4, 6, 8, 10, and 12 mg/m2/day for 14 or 21 days of a 28 day cycle. Safety, efficacy, and pharmacokinetics of tamibarotene were evaluated. RESULTS: Twenty-two patients (median age 8 years) were enrolled in this study. No dose-limiting toxicity (DLT) was encountered, and tamibarotene was generally well tolerated. Two patients experienced severe adverse events (AEs), leading to discontinuation of the treatment. One grade 4 venous thrombosis and one grade 2 erythema multiforme were observed, which promptly resolved after tamibarotene discontinuance. The grade 4 venous thrombosis was a severe AE but not DLT because it occurred after the evaluation period. Pharmacokinetic analyses showed a dose-dependent increase in the maximum drug concentration (Cmax) and area under the concentration-time curve (AUC). None of the patients achieved a complete response or partial response. Seven patients had stable disease lasting longer than 18 weeks. CONCLUSIONS: The recommended dose for phase II study of tamibarotene in pediatric and young adult patients with refractory solid tumors is 12 mg/m2/day for 21 days in a 28 day cycle.

[A case of hyperammonemic encephalopathy in a patient with recurrent colon cancer treated with modified FOLFOX6].

FOLFOX therapy is a commonly used chemotherapeutic regimen against recurrent and unresectable colon cancer. However, its acute neurotoxicity is rare and not well recognized. We herein report a case of mFOLFOX6-induced hyperammonemic encephalopathy in a patient having recurrent colon cancer. A 74-year-old female with a history of sigmoid colon cancer was diagnosed as liver, lung, and peritoneal recurrences by surveillance CT and PET/CT. She was initially treated with modified FOLFOX6 therapy. After completing treatment, she presented with sudden onset of confusion, cognitive disturbances, and repeated seizures. None of the other radiographic examinations and laboratory tests provided an explanation for her symptoms except hyperammonemia. She was treated with branched-chain amino acid solutions and high-volume drip infusion, 6 hours after which the encephalopathy resolved. Clinicians should be aware of the adverse hyperammonemia induced by mFOLFOX6 when patients treated with mFOLFOX6 present with neurological disorders.

Cytomegalovirus colitis after systemic chemotherapy in a patient with recurrent colon cancer: a case report.

INTRODUCTION: The occurrence of cytomegalovirus colitis is well known in immunosuppressed patients, such as neoplastic patients following chemotherapy, although its exact etiology remains unclear. CASE PRESENTATION: We present a case of cytomegalovirus colitis occurring in a 77-year-old man with vomiting and diarrhea 2 weeks after initial systemic chemotherapy consisting of 5-fluorouracil, leucovorin and irinotecan for a recurrent colorectal cancer. Initial colonoscopy revealed multiple punched-out ulcers in the transverse colon and the diagnosis of cytomegalovirus was based on positive cytomegalovirus antigen detected by indirect enzyme antibody method, although immunohistological examination of tissues biopsied at colonoscopy was negative. The symptoms ceased under ganciclovir and octreotide treatment, and the patient recovered gradually. CONCLUSION: The most probable cause of the cytomegalovirus colitis in this case was impaired immunity following chemotherapy. Cytomegalovirus infection should be included in the differential diagnosis of gastrointestinal disease in colorectal cancer patients after chemotherapy and, when suspected, the clinician should pursue appropriate diagnostic interventions including colonoscopy.

[Marked response to S-1 chemotherapy for para-aortic lymph node metastasis arising from gastric cancer].

We report a recurrent case of gastric cancer with para-aortic lymph node metastasis that showed a marked response to systemic chemotherapy consisting of S-1 alone. A 70-year-old male was admitted to our hospital with appetite loss and left abdominal pain. He had a history of distal gastrectomy due to the advanced gastric cancer. Endoscopy revealed a submucosal tumor-like elevation with central ulcer, and the biopsy specimen was poorly-differentiated adenocarcinoma histologically. CT of the abdomen demonstrated a para-aortic lymph node swelling behind the remnant stomach, indicating an unresectable recurrent gastric cancer. We initially treated the patient with S-1 chemotherapy (60 mgx2/day) by oral administration. His tumor immediately responded to the chemotherapy, and restaging abdominal CT after 2 cycles of chemotherapy showed almost complete regression of lymph node metastasis. The patient has undergone S-1 chemotherapy and currently has remained in remission for more than 21 months with no severe adverse events. The S-1 regime was effective and safe, suggesting that S-1 could be the first-line chemotherapy for recurrent gastric cancer.