thioguanine-anhydrous and Stomach-Neoplasms

In a phase II study, 18 patients with advanced gastric carcinoma were treated with intravenous 6-thioguanine. A 30-minute infusion of 55 mg/m2 (starting dose) was administered once a day for 5 consecutive days, the courses being repeated every 5 weeks. A median of 2 courses (range, 1-4) was administered. Among the 18 patients, 17 having measurable cancer and optimum follow-up were fully assessable for response. None of the patients achieved a complete or partial response. One patient achieved a transient minor response (15 weeks) of the primary gastric carcinoma but the metastatic carcinoma was unchanged. One patient had no change in his measurable carcinoma, and the other 15 patients had progressive disease while receiving intravenous-6-thioguanine. Myelosuppression, although frequent, was mild to moderate at these doses and did not result in significant morbidity. Nonhematologic toxicities were also mild. Our data suggest that intravenous 6-thioguanine given at this schedule is ineffective in previously untreated patients with advanced gastric carcinoma.

Topics: Adult; Aged; Drug Evaluation; Female; Humans; Infusions, Intravenous; Male; Middle Aged; Stomach Neoplasms; Thioguanine

Patients with a wide range of gastrointestinal cancers have been treated with nitrosoureas by the Eastern Cooperative Oncology Group. Methyl-CCNU, CCNU, and streptozotocin have been evaluated as single agents in the treatment of colorectal carcinoma. Methyl-CCNU has had an extensive trial in gastric carcinoma as a single agent and in combination with 5-fluorouracil (5-FU). It has also been used to treat pancreatic carcinoma and, in a few patients, carcinoma of the biliary tract. In gastric cancer it would appear that a synergistic effect on response rates has resulted from the combination of methyl-CCNU and 5-FU. The addition of cyclophosphamide to this combination as an induction agent detracted significantly.

Topics: Clinical Trials as Topic; Colonic Neoplasms; Cyclophosphamide; Drug Evaluation; Drug Therapy, Combination; Fluorouracil; Gastrointestinal Neoplasms; Humans; Lomustine; Nitrosourea Compounds; Rectal Neoplasms; Semustine; Stomach Neoplasms; Thioguanine

Though various therapeutic strategies have been developed to overcome gastric cancer, the overall prognosis and therapeutic effect are still not optimistic. As a novel identified type of cell death, ferroptosis has been considered as a promising tumor suppression mechanism with therapeutic potential against gastric cancer. In this work, we screened a collection of 4890 bioactivity compounds and committed to find novel agents that can induce apoptosis in gastric cancer. Among these compounds, 6-TG was identified as a potential ferroptosis inducer in gastric cancer cells for the first time. It could inactivate system xc

Topics: Apoptosis; Cell Line, Tumor; Drug Repositioning; Ferroptosis; Humans; Stomach Neoplasms; Thioguanine

The results obtained with very intensive treatment in previously untreated patients early in the disease are encouraging, and we hope will change the philosophy of most investigators that even in far advanced disease such as those with marrow metastases or multiple primary sites, one can still obtain complete regression at all tumour sites within 1 to 1 1/2 months from onset of therapy by combined treatment with multiple chemotherapeutic agents and radiation therapy to one or more sites.

Topics: Adolescent; Antineoplastic Agents; Asparaginase; Bone Neoplasms; Child; Child, Preschool; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Hydroxyurea; Leukemia; Leukemia, Lymphoid; Lymph Nodes; Lymphoma; Male; Mediastinal Neoplasms; Methotrexate; Nasopharyngeal Neoplasms; Ovarian Neoplasms; Skin Neoplasms; Stomach Neoplasms; Thioguanine; Vincristine