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Background: Hyponatremia in cancer patients is often caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The aim of this observational multicenter study was to analyze the medical and economic implications of SIADH in this setting. Methods: This study included 90 oncological patients from 28 Italian institutions that developed SIADH between January 2010 and September 2015. Data on clinical–pathological characteristics, anticancer therapies, hyponatremia, and related treatments were statistically analyzed. Results: The majority were lung cancer patients (73%) with metastatic disease at the onset of hyponatremia (83%). A total of 76 patients (84%) were hospitalized because of SIADH and less than half (41%) received tolvaptan for SIADH treatment. The duration of hospitalization was significantly longer in patients who did not receive tolvaptan and in those who do not reach sodium normalization during hospitalization. Patients who experienced a second episode of hyponatremia following tolvaptan dose modification/discontinuation presented a significantly lower serum sodium value at the time of hospitalization and minimum sodium value during hospitalization compared with patients who had not experienced another episode. The severity of hyponatremia, defined as minimum sodium value during hospitalization with a cut-off value of 110 mmol/l, and not obtaining sodium correction during hospitalization significantly correlated with overall survival rate. Conclusions: Hyponatremia due to SIADH could result in longer hospitalization and in a decreased overall survival when not adequately treated, and tolvaptan represents an effective treatment with a potential effect of both improving overall survival and decreasing duration of hospitalization.

BACKGROUND The objective of the current study was to define the activity and tolerability, as well as the influence on resectability, of the combination of gemcitabine, paclitaxel, and cisplatin (GTP) as induction chemotherapy for patients with Stage IIIA(N2) nonsmall cell lung carcinoma (NSCLC). METHODS Forty-nine chemotherapy-naive patients (median age, 61 years; World Health Organization performance status, 0–1) with biopsy-proven Stage IIIA(N2) disease received 1000 mg/m2 gemcitabine, 125 mg/m2 paclitaxel, and 50 mg/m2 cisplatin on Days 1 and 8 of every 3 weeks until reevaluation for surgery or definitive radiotherapy. RESULTS Grade 3–4 neutropenia was the most common hematologic toxicity, occurring in 32.7% of patients; however, only 1 case of febrile neutropenia was reported. Grade 3–4 thrombocytopenia occurred in 12.2% of patients but was not associated with bleeding. Severe nonhematologic toxicities were uncommon; the only Grade 4 nonhematologic toxicity was diarrhea, which occurred in 4% of patients. One patient died after the first course of therapy, but this event was found to be unrelated to treatment. Thirty-six patients (73.5%) achieved an objective response, and an additional 4 patients had stable disease with clearance of mediastinal lymph nodes. Overall, 29 patients underwent thoracotomy and 27 (55%) underwent complete resection. Mediastinal nodes were free of tumor in 35% of all cases, and 8 pathologic complete responses (16%) were reported. Median survival was 23 months, with a 1-year survival rate of 85%. CONCLUSIONS GTP is highly active as an induction chemotherapy regimen for Stage IIIA(N2) NSCLC and yields good toxicity results. The use of GTP in combination with radiotherapy and new biologic drugs should be explored. Cancer 2003. © 2003 American Cancer Society. DOI 10.1002/cncr.11662

1 Anatomic Pathology Unit, San Camillo-Forlanini Hospital, Rome, Italy 2 Department of Cardiovascular and Respiratory Sciences, San Camillo-Forlanini Hospital, Rome, Italy 3 Thoracic Surgery Unit, San Camillo-Forlanini Hospital, Rome, Italy Medical Oncology Unit, San Camillo-Forlanini Hospital, Rome, Italy 5 1st Oncological Pulmonary Unit, San Camillo-Forlanini Hospital, Rome, Italy 6 2nd Oncological Pulmonary Unit, San Camillo-Forlanini Hospital, Rome, Italy

Two hundred sixteen patients with unresectable non-small cell lung carcinoma were randomly allocated to receive etoposide (120 mg/m2, days 1-3) either alone or in combination with high-dose cisplatin (60 mg/mz, days 1-2). The patients’ distribution and characteristics were similar in the two treatment arms. The objective response rate for etoposide was 7% versus 25.8% for etoposide plus cisplatin (P < 0.005). Median progression-free survival in etoposide arm was 3.5 months versus 5 months in the combination arm (P = 0.43). The median survival time for etoposide was 6 months compared with 8 months for etoposide combined with cisplatin (P = 0.87). Significantly more nausea/vomiting (P < 0.005), serum creatinine elevation (P < 0.0051, hearing loss and/or tinnitus (P < 0.005), peripheral neuropathy (P < 0.005), leukopenia (P < 0.025), and anemia (P < 0.005) occurred in the etoposide plus cisplatin arm. No statistically significant difference was recorded between the two arms in terms of performance status changes. In conclusion the addition of high-dose cisplatin to single-agent etoposide significantly increases the chance of obtaining tumor response in advanced non-small cell lung cancer at the cost of an increased toxicity without any significant long-term impact on survival and progression-free survival. Cancer 66:130-134,1990. HE TREATMENT of inoperable non-small cell lung

Malignant pleural mesothelioma represents a rare disease, for which chemotherapy actually remains unsatisfactory. From August 1998 to November 2001, 28 chemo-radio-immunonaive patients were consecutively enrolled in the trial: 22/6 males/females; median age 63 years (range, 45-79); median ECOG PS 1 (range, 0-2). They were treated with epirubicin (100 mg/m2 iv on day 1) plus gemcitabine (1000 mg/m2 iv on days 1 and 8) every 4 weeks for 6 cycles. Patients who responded to chemotherapy (n = 6) were subsequently treated with interleukin-2 (4,500,000 IU) subcutaneously every other day, until progression. A total of 124 epirubicin-gemcitabine cycles were administered (median, 6/patient; range, 2-6). Twenty-six patients were evaluated for toxicity. According to WHO criteria, we observed grade III-IV hematological and gastrointestinal toxicity respectively in 3 patients (11%) and 1 patient (3%). No red cell transfusions were required and no toxic deaths occurred. Two patients (8%) could not be evaluated for response (no therapy performed). According to WHO criteria, the final responses were: partial in 4 patients (14%), stable disease in 19 patients (69%), and progression in 3 patients (10%). In 26 patients, the median survival was 55 weeks (range, 7-222) and median time to progression 30 weeks (range, 4-156). At the time of this writing, no patient is alive. The 1-year survival was 32%, 2-year survival 11%, and 4% at 3 and 4 years. All patients were at stage III, and time to progression was 58 weeks and survival 63.5 weeks, without any toxicity. This multi-center phase II clinical trial showed that epirubicin plus gemcitabine, as a first-line treatment in malignant pleural mesothelioma, has promising activity with a good tolerability profile and symptom palliation. The role of interleukin-2 in maintenance therapy for malignant pleural mesothelioma is encouraging and requires further study.

Twenty-six patients with advanced bronchogenic adenocarcinoma or large cell carcinoma were treated by combination chemotherapy consisting of Ftorafur, adriamycin and mitomycin C (FAM II). The patients had not received prior chemotherapy and were not eligible for radiotherapy and surgery. The overall response rate was 25% (5 of 20 patients). One patient with adenocarcinoma achieved a complete response, four achieved a partial response and three a minor response. In four patients the disease was stable. The response did not vary strictly with initial performance status as patients with a Karnofsky score of less than 70% also showed a median survival of 7.5+ months. The FAM II combination was very well tolerated, particularly regarding nausea and vomiting; the latter occurred in only one patient. No patient required a reduction in the drug dose because of leukopenia or thrombocytopenia.