YOU ARE NOW CONNECTED TO THE TOXLINE (1981 FORWARD, NON-ROYALTY) FILE. ==PANCREATIC AND GEMCITABINE== 1 AUTHOR Hui YF AUTHOR Reitz J TITLE Gemcitabine: a cytidine analogue active against solid tumors. SOURCE Am J Health Syst Pharm; VOL 54, ISS 2, 1997, P162-70; quiz 197-8 (REF: 69) ABSTRACT The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of gemcitabine are reviewed. Gemcitabine is a deoxycytidine-analogue antimetabolite with activity against some solid tumors. Gemcitabine is phosphorylated intracellularly to difluorodeoxycytidine triphosphate, which terminates DNA-chain elongation and competitively inhibits DNA polymerase and ribonucleotide reductase. After i.v. administration, gemcitabine is rapidly distributed into total body water. The drug is deaminated in the plasma to inactive difluorodeoxyuridine; both gemcitabine and difluorodeoxyuridine are primarily renally eliminated. In clinical studies, gemcitabine reduced pain and improved function in patients with advanced pancreatic cancer. Gemcitabine has shown some activity against non-small-cell lung cancer, particularly when combined with cisplatin or ifosfamide. The agent has also shown modest activity against advanced ovarian and breast cancer. Adverse effects include dose-limiting myelosuppression, flu-like symptoms, nausea, vomiting, and rash. Gemcitabine has FDA-approved labeling for use in the treatment of locally advanced and metastatic pancreatic cancer. The recommended dosage for this indication is 1000 mg/m2 (as the hydrochloride salt) i.v. given over 30 minutes weekly for seven weeks, followed after one week of rest by 1000 mg/ m2 i.v. given over 30 minutes weekly for three weeks every four weeks. Gemcitabine palliates symptoms in patients with advanced or metastatic pancreatic cancer. More study is needed to determine gemcitabine's role in the treatment of non-small-cell lung cancer, ovarian cancer, and breast cancer. 2 AUTHOR Rothenberg ML TITLE New developments in chemotherapy for patients with advanced pancreatic cancer. SOURCE Oncology (Huntingt); VOL 10, ISS 9 Suppl, 1996, P18-22 (REF: 25) ABSTRACT Alleviation of tumor-related symptoms may be a more appropriate basis for judging drug efficacy in pancreatic cancer than is tumor shrinkage. Clinical benefit response (CBR), a new way to assess clinical efficacy based on marked, sustained improvement in pain intensity, analgesic consumption, and performance status, was used to evaluate a new chemotherapeutic agent, gemcitabine (2',2'-difluorodeoxycytidine [Gemzar]). A phase III study of newly diagnosed pancreatic cancer patients treated with either gemcitabine or fluorouracil (5-FU) and a phase II trial of gemcitabine in patients whose disease had progressed despite prior treatment with 5-FU both demonstrated that a significant number of patients achieved a CBR with gemcitabine. Prolonged survival was a secondary benefit demonstrated in the phase III trial. In both studies, gemcitabine was well tolerated, with a relatively mild toxicity profile. These results suggest that gemcitabine may serve as a prototype for the development of more effective therapies for pancreatic cancer patients. 4 AUTHOR Sakata Y AUTHOR Takemori H AUTHOR Suzuki H TITLE [Chemotherapy for pancreatic cancer] SOURCE Gan To Kagaku Ryoho; VOL 23, ISS 12, 1996, P1647-50 (REF: 19) ABSTRACT Few antitumor agents are effective for advanced pancreatic cancer. 5-fluorouracil, doxorubicin, epirubicin, and mitomycin C were tested as single agents for their respective efficacy against pancreatic cancer. Their response rates were 15, 12, 24 and 24%, respectively. Several trials of combination chemotherapy using mitomycin C, doxorubicin and 5-FU (FAM) were performed, but their response rates did not go exceed those of single agents. Recently, the goal of chemotherapy for pancreatic cancer is thought to be quality of life. Combination of 5-FU and cisplatin or 5-FU, leucovorin and alpha interferon were effective for the prolongation of life with less toxicities. Their median survival times were 7.6 months, and 22 months in PR cases, respectively. CPT-11, gemcitabine, taxotere and BOF-A2 are promising new drugs for their effectiveness and benefits for patients with pancreatic cancer. Combination of mitomycin C, carboquone and 5-FU with angiotensin II was effective in terms of antitumor effect and prolongation of life. Generally, a large number of patients with advanced pancreatic cancer cannot receive chemotherapy because of deterioration in performance status. For them, combination of continuous venous infusion of low-dose 5-FU and low-dose cisplatin could be effective. The majority of patients with pancreatic cancer must await new agents and methodology in the future. 5 AUTHOR Moore M TITLE Activity of gemcitabine in patients with advanced pancreatic carcinoma. A review. SOURCE Cancer; VOL 78, ISS 3 Suppl, 1996, P633-8 (REF: 21) ABSTRACT BACKGROUND: In early phase II trials in advanced pancreatic cancer, gemcitabine demonstrated modest antitumor activity. The investigators in these studies reported that gemcitabine should be studied further in view of the degree and frequency of symptomatic improvement observed, the durability of some of the remissions, and the favorable toxicity profile. METHODS: In order to quantify such symptomatic improvement, a rigorous endpoint of Clinical Benefit was developed that incorporated measures including pain intensity, analgesic consumption and performance status, which have been shown to be reliable and valid endpoints in other studies. RESULTS: Two trials have been conducted using this methodology in patients with advanced pancreatic carcinoma. CONCLUSIONS: The results of these studies suggest that gemcitabine is the first cytotoxic agent with any meaningful impact on survival and disease-related symptoms in advanced pancreatic adenocarcinoma. The degree of improvement seen is one which patients with cancer often consider to be most important. Further studies will be required to define more fully the role of gemcitabine in the treatment of pancreatic cancer.