isotretinoin and Hypercalcemia

Topics: Alkalosis; Benzothiadiazines; Calcinosis; Cholecalciferol; Diuretics; Humans; Hypercalcemia; Hyperparathyroidism; Isotretinoin; Lithium; Osteitis Deformans; Sarcoidosis; Sodium Chloride Symporter Inhibitors; Tamoxifen; Tretinoin; Vitamin A

Treatment of neuroblastoma cell lines with 13-cis-retinoic acid (cis-RA) can cause sustained inhibition of proliferation. Since cis-RA has demonstrated clinical responses in neuroblastoma patients, it may be effective in preventing relapse after cytotoxic therapy. This phase I trial was designed to determine the maximal-tolerated dosage (MTD), toxicities, and pharmacokinetics of cis-RA administered on an intermittent schedule in children with neuroblastoma following bone marrow transplantation (BMT).. Fifty-one assessable patients, 2 to 12 years of age, were treated with oral cis-RA administered in two equally divided doses daily for 2 weeks, followed by a 2-week rest period, for up to 12 courses. The dose was escalated from 100 to 200 mg/m2/d until dose-limiting toxicity (DLT) was observed. A single intrapatient dose escalation was permitted.. The MTD of cis-RA was 160 mg/m2/d. Dose-limiting toxicities in six of nine patients at 200 mg/m2/d included hypercalcemia (n = 3), rash (n = 2), and anemia/thrombocytopenia/emesis/rash (n = 1). All toxicities resolved after cis-RA was discontinued. Three complete responses were observed in marrow metastases. Serum levels of 7.4 +/- 3.0 mumol/L (peak) and 4.0 +/- 2.8 mumol/L (trough) at the MTD were maintained during 14 days of therapy. The DLT correlated with serum levels > or = 10 mumol/L.. The MTD of cis-RA given on this intermittent schedule was 160 mg/m2/d. Serum levels known to be effective against neuroblastoma in vitro were achieved at this dose. The DLT included hypercalcemia, and may be predicted by serum cis-RA levels. Monitoring of serum calcium and cis-RA levels is indicated in future trials.

Topics: Bone Marrow Transplantation; Child; Child, Preschool; Combined Modality Therapy; Female; Humans; Hypercalcemia; Isotretinoin; Male; Neuroblastoma; Remission Induction

13-cis-Retinoic acid (13-cisRA) is used as a postconsolidation treatment in patients with high-risk neuroblastoma. Hypercalcemia is a known side effect of retinoids. Frequency, symptoms, treatment, and risk factors for hypercalcemia were analyzed.. Data were retrospectively analyzed for 350 patients registered in the German Neuroblastoma trials NB97 and NB04 who were treated with high-risk protocols-including myeloablative chemotherapy with autologous stem cell transplantation (SCT) or maintenance therapy-and had received 13-cisRA between January 1, 2000 and December 31, 2010.. Hypercalcemia was reported in 78 patients (22.3%), and 37 patients (10.6%) developed Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or 4 hypercalcemia. The calcium levels were 2.5-4.6 mmol/L (median 3.1 mmol/L). Patients with a single kidney were at a higher risk of developing hypercalcemia (p = .001). Regarding postinduction treatment, 69 of 280 patients with SCT (24.6%) and nine of 70 patients without SCT (12.9%) developed hypercalcemia during 13-cisRA treatment (p = .037). Most patients developed hypercalcemia in the first cycle of 13-cisRA, and only in a single cycle. Hypercalcemia symptoms were frequent but moderate. In most patients, treatment with 13-cisRA was continued without dose reduction in subsequent cycles.. In this cohort, grades 3 and 4 hypercalcemia were observed more often than previously reported. A single kidney and pretreatment with myeloablative chemotherapy with stem cell transplantation were identified as potential risk factors for the development of hypercalcemia.

Topics: Drug-Related Side Effects and Adverse Reactions; Female; Hematopoietic Stem Cell Transplantation; Humans; Hypercalcemia; Isotretinoin; Male; Neuroblastoma; Retrospective Studies; Solitary Kidney; Transplantation, Autologous

Scrotal calcinosis is a rare disorder characterized by multiple papules or nodules of calcification in the scrotal skin. The pathogenesis of this disease is poorly understood. The condition presents as several brown to yellowish asymptomatic nodules on the scrotum. Excision followed by scrotal reconstruction is the treatment of choice. It leaves a good cosmetic result with low chances of recurrence. Newer treatments, such as ablative lasers, have been proposed with very good results. We describe the case of a 28-year-old patient with a history of severe acne treated with oral isotretinoin that presented for scrotal nodules. On laboratory examination, hypercalcemia was found with normal phosphorus, parathyroid hormone, and vitamin D hormone levels. Hypercalcemia was linked to his isotretinoin therapy. Serum calcium concentrations normalized after cessation of isotretinoin and hydration. Because the patient refused surgery, a biopsy of the lesion confirmed the diagnosis of scrotal calcinosis. Then the patient was referred to a cosmetic laser center to treat his condition.

Topics: Adult; Calcinosis; Calcium; Genital Diseases, Male; Humans; Hypercalcemia; Isotretinoin; Male; Parathyroid Hormone; Phosphorus; Scrotum; Vitamin D

13-cis-retinoic acid is an established component of treatment for children with high-risk neuroblastoma. However, significant hypercalcemia is increasingly recognized as a potentially life-threatening dosage-related side effect. We present 2 patients with significant hypercalcemia secondary to 13-cis-retinoic acid and their management, and identified the predictive factors for susceptibility to hypercalcemia. Assessing glomerular filtration rate and concomitant medication help predict individual susceptibility to hypercalcemia. Calcium levels should be monitored at days 1, 7, and 14 of each course of retinoic acid. An algorithm for the management of hypercalcemia during the affected and subsequent cycles of retinoid therapy is proposed.

Topics: Calcium; Child; Child, Preschool; Dermatologic Agents; Disease Management; Female; Glomerular Filtration Rate; Humans; Hypercalcemia; Isotretinoin; Male; Monitoring, Physiologic; Neuroblastoma; Prognosis; Risk Factors

We report 19 episodes of hypercalcemia in three children treated with 13-cis-retinoic acid (13-cis-RA) as a post-consolidation therapy for high-risk neuroblastoma. There was no concomitant overload in 13-cis-RA blood levels. Blood calcium fell after arrest of 13-cis-RA intake. Half dosage retinoid treatment resumption did not prevent the recurrence of hypercalcemia. Concomitant biological values showed massive bone resorption. Hence, hypercalcemia seemed not secondary to 13-cis-RA overload but rather to inter-individual variability in its interaction with bone metabolism. Current guidelines in case of hypercalcemia are to reduce 13-cis-RA dosage. Instead we propose to maintain the therapeutic dosage, but to shorten the duration of courses.

Topics: Bone Resorption; Calcium; Child, Preschool; Female; Humans; Hypercalcemia; Infant; Isotretinoin; Male; Neuroblastoma

A 6-year-old male diagnosed with extensive neuroblastoma was treated with chemotherapy, surgery, autotransplantation, and radiotherapy. He was then enrolled on a study to assess the monoclonal antibody Ch14.18 (anti-GD2) with 13 cis-retinoic acid. 13-cis-retinoic acid therapy caused severe bone pain and hypercalcemia. Bone scans showed multiple osteoblastic lesions suggesting recurrent disease however MIBG scans were negative. Serum markers of bone turnover were increased and the patient required pamidronate therapy to treat persistent hypercalcemia. Retinoic acid toxicity needs to be considered in the differential of painful osteoblastic lesions and/or hypercalcemia. MIBG scans can assist in differentiating from recurrent disease.

Topics: 3-Iodobenzylguanidine; Child; Humans; Hypercalcemia; Isotretinoin; Male; Neoplasm Recurrence, Local; Neuroblastoma; Osteoblasts

Topics: Adrenal Gland Neoplasms; Child; Child, Preschool; Dermatologic Agents; Female; Humans; Hypercalcemia; Isotretinoin; Male; Neuroblastoma; Peritoneal Neoplasms

Hypercalcemia is a potential dosage-related adverse effect of 13-cis-retinoic acid in patients with neuroblastoma. Severe hypercalcemia requiring dosage reduction has been reported in children receiving 13-cis-retinoic acid 200 mg/m2/day and in those with concurrent renal impairment receiving 160 mg/m2/day. A 12-year-old girl without renal dysfunction, diagnosed with neuroblastoma, developed severe hypercalcemia requiring several hospitalizations while receiving 13-cis-retinoic acid 160 mg/m2/day. Her hypercalcemia resolved with hydration, diuretic therapy, and temporary discontinuation of 13-cis-retinoic acid. Despite a 50% dosage reduction to 80 mg/m2/day, severe hypercalcemia recurred with the next treatment cycle. Further treatment with 13-cis-retinoic acid was made tolerable by shortening the duration of the remaining cycles. Serum calcium levels should be monitored in patients with neuroblastoma who receive 13-cis-retinoic acid.

Topics: Brain Neoplasms; Child; Female; Humans; Hypercalcemia; Isotretinoin; Keratolytic Agents; Neoplasm Recurrence, Local; Neuroblastoma

13-cis-Retinoic acid (cis-RA) has efficacy in the treatment and prevention of certain malignancies. In vitro effects against neuroblastoma include induction of differentiation, inhibition of proliferation, and decreased N-myc expression. We hypothesized that cis-RA may be effective against minimal residual disease in neuroblastoma patients. A phase I trial to determine the maximal tolerated dosage and toxicity of cis-RA in pediatric patients with neuroblastoma after bone marrow transplantation was initiated.. Forty-nine pediatric patients (status post-bone marrow transplant for neuroblastoma) were treated for 14 days with oral cis-RA in escalating doses from 100 to 200 mg/m2/day followed by a 14-day rest period for up to 12 months.. In three of 39 patients (7.7%) evaluable for calcium levels, hypercalcemia (12.6-18.7 mg/dl) was the dose-limiting toxicity. Grade 1-3 hypercalcemia occurred in nine of 39 patients (23%). The overall incidence of hypercalcemia was 31% (12 of 39). Only one patient was symptomatic due to the hypercalcemia, with arthralgias and myalgias. The hypercalcemia resolved with temporary discontinuation of the drug and a 25% dose reduction for subsequent courses.. Hypercalcemia is a novel dose-limiting toxicity for cis-RA. Patients receiving high doses of cis-RA should have monitoring of serum calcium levels.

Topics: Antineoplastic Agents; Bone Marrow Transplantation; Calcium; Child; Child, Preschool; Female; Humans; Hypercalcemia; Isotretinoin; Neuroblastoma

Topics: Humans; Hypercalcemia; Isotretinoin; Risk; Tretinoin

Topics: Acne Vulgaris; Administration, Oral; Adult; Humans; Hypercalcemia; Isotretinoin; Male; Tretinoin