5‐FU versus combination therapy with tubercidin, streptozotocin, and 5‐Fu in the treatment of pancreatic carcinomas: COG protocol 7230

Abstract

From May 1972 until May 1976, 105 patients were entered on Central Oncology Group protocol 7230 to compare the combination of streptozotocin, tubercidin, and 5-fluorouracil (5-FU) versus 5-FU alone in the treatment of adenocarcinoma and islet cell carcinoma of the pancreas. Twenty-nine were not evaluable. Thirty-six evaluable cases received 5-FU, and 40 received the combination, with no significant difference in time to progression or survival. Toxicity in the two regimens was somewhat different but was essentially similar in magnitude. Results indicate no benefit in the treatment of adenocarcinoma of the pancreas with the three-drug combination over 5-FU alone. All of the islet cell tumor patients benefited from the combination by response or arrest of progression of disease. Further study should be directed toward the use of this combination in the treatment of functioning and non-functioning islet cell tumors of the pancreas.

Gastrinoma with multiple liver metastases: Effectiveness of dacarbazine (DTIC) therapy

“…5‐Fluorouracil (5‐FU) has also been in common use for the treatment of various cancers. Its effectiveness for the treatment of malignant neuroendocrine tumors seems to be similar to that observed with other gastrointestinal malignant tumors (i.e., pancreatic cancer) 15,16. The most intensively studied combined chemotherapy regimen for malignant neoendocrine tumors has been that of 5‐FU and streptozotocin, with results showing about 60% response rate 17,18…”

“…Its effectiveness for the treatment of malignant neuroendocrine tumors seems to be similar to that observed with other gastrointestinal malignant tumors (i.e., pancreatic cancer). 15,16 The most intensively studied combined chemotherapy regimen for malignant neoendocrine tumors has been that of 5-FU and streptozotocin, with results showing about 60% response rate. 17,18 The mechanism of action of DTIC as an antitumor agent is not yet completely understood, but probably includes an alkylating action and inhibition of DNA synthesis.…”

Enhancement of hemoglobin and F-cell production by targeting growth inhibition and differentiation of K562 cells with ribonucleotide reductase inhibitors (didox and trimidox) in combination with streptozotocin

“…In addition to its free radical activity, trimidox has been shown to prevent ischemia reperfusion injury in an isolated rabbit heart model [31]. Streptozotocin, on the other hand, is a non-myelosuppressive agent with potent antitumor activity against islet carcinomas and malignant carcinoids [13]. In view of frequent blood transfusions in individuals with severe sickle cell disease, iron overload has been a major concern.…”

“…In their in vivo studies, Pace et al observed that administration of didox to transgenic sickle cell mice and an anemic baboon resulted in high level of ␥-globin gene expression [11]. Streptozotocin, on the other hand, is an anti-neoplastic agent that has been in use in combination regimens in cancer chemotherapy [13,14]. One of the unique pharmacological properties of STZ is its antitumor activity without bone marrow toxicity [15].…”

Nucleobase and Nucleoside Analogues: Resistance and Re-Sensitisation at the Level of Pharmacokinetics, Pharmacodynamics and Metabolism

“…Tubercidin, toyocamycin, sangivamycin and derivatives are bacteria-derived adenosine analogues with different effects on RNA and DNA, protein kinase C, microtubules, and nucleophosmin (NPM1) [ 214 , 215 , 216 , 217 , 218 ]. These have been used in small clinical trials, in the case of tubercidin with clinical efficacy [ 219 , 220 , 221 , 222 , 223 , 224 ]. Importantly, differential resistance to these nucleoside analogues has been described in vitro [ 225 ].…”