Gemcitabine following radiotherapy with concurrent 5‐fluorouracil for nonmetastatic adenocarcinoma of the pancreas

Abstract

SUMMARY Gemcitabine has been shown to be an active agent in the treatment of pancreatic cancer. This study was conducted to prospectively examine the tolerance and early efficacy of adjuvant gemcitabine following radiotherapy with concurrent 5-fluorouracil (5-FU) for nonmetastatic pancreatic adenocarcinoma. Twenty-three patients, median age 64 years, were treated with combined modality therapy. Nine patients underwent tumor resection before chemoradiation; 14 patients with locally unresectable tumors received definitive chemoradiation. Radiotherapy utilized four fields to the tumor and lymphatics to 45 Gy, plus a lateral boost to 50.4 Gy. Concurrent 5-FU 500 mg/m 2 /day was administered on days 1-3 and 29-31, followed by 4 months of gemcitabine 1,000 mg/m 2 / week for 3 weeks (fourth week break). Adjuvant gemcitabine was well tolerated. Eightythree percent of the patients completed three to four cycles. The primary dose-limiting toxicity was leukopenia, which was observed in 10 patients (43%). Nonhematologic toxicities were reported in five patients (22%). There were no cases of gemcitabine-induced radiation recall and there have been no deaths attributed to treatment toxicity. Median follow-up for the 23 patients was 12 months (range, 5-50); the actuarial median survival was 13 months. This report confirms that adjuvant gemcitabine following radiotherapy with concurrent 5-FU for nonmetastatic pancreatic adenocarcinoma can be safely administered.

Combined 90Yttrium‐DOTA‐labeled PAM4 antibody radioimmunotherapy and gemcitabine radiosensitization for the treatment of a human pancreatic cancer xenograft

“…[42][43][44] Although few patients are deemed to have resectable disease, recent studies have suggested that these patients may also benefit from a program of preoperative chemoradiation. [3][4][5][6][7][8][9] Those patients given preoperative chemoradiation had significantly higher numbers of disease-free margins and fewer numbers of involved lymph nodes at surgery than their counterparts treated with "curative resection" alone. Overall, the use of chemoradiation procedures has provided a modest increase in median survival time.…”

“…74 Moreover, a preponderance of clinical data show the combination to be well tolerated. [3][4][5][6][7][8][9]11,12 Since we were administering 90 Y-DOTA-cPAM4 concurrently with gemcitabine, toxicity to the intestine was a distinct possibility. However, 90 Y-PAM4 is cleared rapidly from the blood (t 1/2 ϭ28 hr) and our previous biodistribution data show that very little radiation is absorbed by the small intestine (135 cGy at 100 Ci injected dose), and therefore should not be toxic in these mice.…”

“…Gemcitabine may be useful in this regard since it is a potent radiosensitizer. 2 External beam radiotherapy combined with gemcitabine chemotherapy has been studied in patients with both resectable [3][4][5][6][7][8][9] and nonresectable tumors, 10 -12 with minimal toxicity. Although palliation of disease symptoms has been beneficial, only a moderate increase in median survival has been observed.…”

Radiotherapy in Pancreatic Cancer

“…Recent phase II-studies and cohort studies employing CRT reported median overall survival times of 10-11 months and 1-year-survival rates of up to 40% [16,28,30,39,52]. The value and particularly the toxicity of additive chemotherapy after CRT have to be further assessed in studies [11,26,30].…”

Combined therapy of experimental pancreatic cancer with CYP2B1 producing cells: Low-dose ifosfamide and local tumor irradiation

“…2,3 The cytotoxic drugs 5-fluorouracil, cisplatin and gemcitabine belong to the basic chemotherapeutic agents in the treatment of this malignant disease. 1,4,5 Ifosfamide represents an alternative agent that is effective in the therapy of pancreatic cancer. 6 The noncytotoxic prodrug is metabolized by liver enzymes, such as cytochrome P450 2B1 (CYP2B1), to its active metabolites.…”