sirolimus and Carcinoma--Medullary

This phase II study investigated the efficacy and safety of everolimus, an inhibitor of mammalian target of rapamycin (mTOR), in locally advanced or metastatic thyroid cancer.. Patients with thyroid cancer of any histology that was resistant or not appropriate for (131)I received everolimus 10 mg daily orally until unacceptable toxicity or disease progression. The primary end point was disease control rate [partial response (PR) + stable response ≥12 weeks]. Secondary end points included response rates, clinical benefit (PD + durable stable disease (SD)], progression-free survival (PFS), overall survival, duration of response, and safety.. Thirty-eight of 40 enrolled patients were evaluable for efficacy. The disease control rate was 81% and two (5%) patients achieved objective response; their duration of response was 21+ and 24+ weeks. Stable disease (SD) and progressive disease was reported in 76% and 17% of patients, respectively. Seventeen (45%) patients showed durable SD (≥24 weeks) and clinical benefit was reported in 19 (50%) patients. Median PFS was 47 weeks [95% confidence interval (CI) 14.9-78.5]. Calcitonin, CEA, and thyroglobulin concentrations were ≥50% lower than baseline in three (30%) and four (44%) patients with medullary thyroid cancer and five (33%) patients with PTC, respectively. The most common treatment-related adverse events were mucositis (84%), anorexia (44%), and aspartate transaminase/alanine transaminase elevation (26%).. Everolimus had a limited activity with low response rate in locally advanced or metastatic thyroid cancer. Reasonable clinical benefit rate and safety profile may warrant further investigation.. NCT01164176.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Medullary; Carcinoma, Papillary; Disease-Free Survival; Everolimus; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Staging; Sirolimus; Thyroid Neoplasms; Treatment Outcome

A 53-year-old female patient presented with cough and hoarseness for 3 years. Based on a biopsy of a bronchial tumor, a small cell neuroendocrine tumor of the lung was diagnosed and chemotherapy with etoposide and cisplatin was initiated. As the tumor progressed under chemotherapy, the bronchial biopsy was reevaluated and further biopsies of liver and adrenal metastases were obtained. The diagnosis was corrected, and an atypical neuroendocrine bronchial carcinoma was diagnosed. Under octreotide therapy, the patient remained stable for 1 year, when a discrete progress of the primary tumor in the lung was observed. Treatment with the mTOR (mammalian target of rapamycin) inhibitor everolimus was then initiated. Based on this case, the diagnostic criteria, prognostic factors and therapeutic options of neuroendocrine bronchial carcinomas are discussed.

Topics: Adrenal Gland Neoplasms; Adrenal Glands; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Bone Neoplasms; Calcitonin; Carcinoma, Bronchogenic; Carcinoma, Medullary; Carcinoma, Neuroendocrine; Cell Division; Female; Humans; Ki-67 Antigen; Liver; Liver Neoplasms; Lung; Lung Neoplasms; Middle Aged; Neoplasm Staging; Neoplasms, Multiple Primary; Octreotide; Paraneoplastic Syndromes; Sirolimus; Thyroid Gland; Thyroid Neoplasms