levoleucovorin and Inappropriate-ADH-Syndrome

BACKGROUND Cisplatin/5-fluorouracil therapy is the standard therapy for unresectable and recurrent esophageal cancer. Cisplatin-based chemotherapy often causes adverse effects, such as nausea, vomiting, and renal dysfunction, which may necessitate dose modification or treatment prolongation. Therefore, novel combination therapies are urgently needed to improve the efficacy and overcome drug toxicity in this setting. CASE REPORT A 77-year-old man with advanced esophageal cancer received cisplatin/5-fluorouracil therapy as neoadjuvant chemotherapy. On day 8 of administration, the patient had lightheadedness, diaphoresis, and nausea and became unconscious and developed severe hyponatremia. We diagnosed the patient with cisplatin-induced syndrome of inadequate antidiuretic hormone secretion (SIADH). Subsequently, water restriction was started, and treatment with a salt-added diet and 3% hypertonic saline infusion was initiated. The hyponatremia improved and the patient was discharged on day 16 of administration. Therefore, neoadjuvant chemotherapy was discontinued, and surgical treatment was performed. However, the tumor recurred and chemotherapy was required. The patient developed severe hyponatremia while receiving neoadjuvant chemotherapy; hence, folinic acid, fluorouracil, and oxaliplatin therapy (FOLFOX) were administered as an alternative treatment. The patient completed the FOLFOX therapy without developing SIADH. CONCLUSIONS The cisplatin/5-fluorouracil therapy is currently the standard chemotherapy regimen for esophageal cancer. However, SIADH is a known adverse effect when using cisplatin. In patients with esophageal cancer, oxaliplatin appears to have a lower risk of SIADH than cisplatin, suggesting that oxaliplatin can be a therapeutic option for patients with esophageal cancer who are at high risk of SIADH.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Esophageal Neoplasms; Fluorouracil; Humans; Inappropriate ADH Syndrome; Leucovorin; Male; Neoadjuvant Therapy; Neoplasm Recurrence, Local; Oxaliplatin; Vasopressins

Ninety-eight patients with small cell carcinoma of the bronchus (SCCB) were treated with a combination of cyclophosphamide, methotrexate with calcium leucovorin rescue, and lomustine (CCNU). VP-16-213 was given on relapse. Response rate and survival were analyzed according to extent of tumor, presence of the syndrome of inappropriate antidiuretic hormone production (SIADH), and, in 38 patients, size of intrathoracic tumor as measured by computerized tomographic (CT) scanning. The median survival of the entire group was 34.6 weeks. In patients with limited disease the median survival was 46 weeks compared to 29 weeks for those with extensive disease. This difference in survival between patients with limited and extensive disease was most marked in those showing a partial response (median survival, 45.9 and 28 weeks, respectively). Patients with ectopic antidiuretic hormone production had a poor prognosis even if they had achieved a complete response. Only one partial response to VP-16-213 occurred. There was a strong correlation between initial intrathoracic tumor size as assessed by total cross-sectional area on CT scan and response and survival. When the total area exceeded 30 cm2 there were no complete responders, but there were complete responses in eight of 21 patients when the area was less than 30 cm2. The relationship between intrathoracic tumor size and response rate was present when analyzed according to disease extent, age, sex, and performance status. A clear relationship between total tumor area and survival was also found. When SCCB is treated with chemotherapy alone, the prognosis is better for those patients who present with limited disease, without SIADH, and with small intrathoracic tumor. In this group it is possible that further intensification of therapy may result in prolonged survival.

Topics: Adult; Aged; Antineoplastic Agents; Carcinoma, Small Cell; Cyclophosphamide; Drug Therapy, Combination; Etoposide; Female; Humans; Inappropriate ADH Syndrome; Leucovorin; Lomustine; Lung Neoplasms; Male; Methotrexate; Middle Aged