An investigational new drug treatment program for patients with gemcitabine

Abstract

BACKGROUND An Investigational New Drug (IND) treatment program allows patients access to a drug that has shown activity against a serious or life‐threatening disease prior to full Food and Drug Administration (FDA) review and approval. This treatment IND program, in which patients with locally advanced or metastatic pancreatic carcinoma were treated with gemcitabine, began in 1995. METHODS Eligibility criteria were ≤1 prior chemotherapy regimen; a Karnofsky performance status (KPS) of ≥50; and adequate bone marrow, liver, and renal function. Gemcitabine was given at a dose of 1000 mg/m2 weekly × 7 followed by a week of rest, then weekly × 3 every 4 weeks thereafter. In this program, disease‐related symptom improvement (DRSI) was defined retrospectively as 1) improvement in pain (on a 7‐point scale) and/or analgesic class (e.g., morphine improving to codeine) and/or KPS (≥20 points), or 2) stability of these three parameters with a 7% increase in weight from baseline. RESULTS A total of 3023 patients enrolled. At baseline, 80% of them had Stage IV disease, and 84% had a baseline KPS ≥ 70. The median age was 65 years, and 56% of the patients were male. The cumulative DRSI response rate after the fourth cycle was 18.4%. Of 982 patients with tumor response data, there were 14 with complete response and 104 with partial response, for an overall response rate of 12.0% (95% confidence interval [CI], 10.0–14.0%). For 2380 patients with survival data, the median survival was 4.8 months (95% CI, 4.5–5.1 months) and the 12‐month survival was 15%. Gemcitabine was well tolerated; only 4.6% of discontinuations were due to adverse events. CONCLUSIONS Notable disease‐related symptom improvement and survival were seen with gemcitabine in this large, compassionate‐use setting, and these findings were in agreement with those of earlier registration trials. Cancer 1999;85:1261–8. © 1999 American Cancer Society.

Escin augments the efficacy of gemcitabine through down-regulation of nuclear factor-κB and nuclear factor-κB-regulated gene products in pancreatic cancer both in vitro and in vivo

“…Gemcitabine, the best chemotherapeutic agent available for the treatment for advanced pancreatic cancer, alone is not very eVective and is associated with systemic toxicity and chemoresistance (Storniolo et al 1999;Moore et al 2007;Diaz-Rubio 2004). It was still unknown whether escin could potentiate the antitumor activity of gemcitabine against pancreatic cancer.…”

Survival after surgical management of pancreatic adenocarcinoma: does curative and radical surgery truly exist?

“…Clinical benefit response, however, can underestimate the effects of chemotherapy because it does not include the assessment of other symptoms. Furthermore, it can overestimate the results of chemotherapy, the reason for this being that it does not properly assess the side effects [75,76]. Therefore, quality of life (QOL) studies have been introduced in the latest adjuvant clinical trials.…”

Concurrent Chemoradiotherapy for Advanced Pancreatic Cancer

“…Through several phase III trials, GEM has been indicated as a first-line treatment for patients with advanced pancreatic cancer including metastatic tumor, because it improves survival [28] and has clinical advantages (pain reduction, improved performance status, weight gain) over 5-FU treatment [6,19].…”