Journal of Clinical Oncology, 2004 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 22, No 14S (July 15 Supplement), 2004: 2140
© 2004 American Society of Clinical Oncology

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Abstract

Management of hyperglycemia in patients with metastatic pancreatic cancer receiving UCN-01 and fluorouracil

Memorial Sloan-Kettering Cancer Center, New York, NY

2140

Background: UCN-01 is associated with dose-limiting hyperglycemia (HG). It is postulated that UCN-01-induced HG may be related to inhibition of AKT-mediated pathways, which play an important role in glucose metabolism. Management of HG is an important consideration in the development of UCN-01. Methods: We evaluated relative changes in insulin sensitivity as a function of treatment in patients with pancreatic cancer enrolled in a phase II study of fluorouracil and UCN-01. Fasting plasma samples were collected on days 1 (pre-FU), 2 (pre-UCN-01), 5 (post-UCN-01) and 16 (mid-cycle) in the first cycle and days 1, 2, 3, and 16 in the second cycle of treatment and analyzed for glucose and insulin levels. Insulin sensitivity was evaluated using the simple QUICKI index (1/log₁₀ insulin + log₁₀ glucose). Patients with HgbA1c 8.0 or fasting glucose 126 were referred to an endocrinologist. Results: We have enrolled 11 patients (median age 60, range 51–77) to this phase II study: 8 are evaluable for response and 11 are evaluable for insulin sensitivity. We observed grade 3 (n=4) or grade 4 (n=1) HG in 5 of the initial 6 patients; two required hospitalization, one with concurrent gram-negative sepsis. Subsequent patients were seen by an endocrinologist to learn self-administration of insulin, with no further grade 3 or 4 HG observed. Compared to baseline (pre-UCN-01), the mean decrease in QUICKI following UCN-01 infusion was 0.085 ± 0.037, indicating increased insulin resistance following UCN-01. In 7 of 8 patients evaluable for response, insulin sensitivity returned to baseline prior to UCN-01 in the 2^nd cycle (day 30); we observed no objective responses. In contrast, 1 patient with persistent increased insulin resistance prior to the 2^nd UCN-01 dose had stable disease for 5 months. Two patients await response evaluation. Conclusion: HG from UCN-01 can be controlled with aggressive glucose monitoring and insulin injections in a pancreatic cancer population. The QUICKI index represents a simple method to monitor insulin resistance in patients receiving UCN-01 therapy and may represent a marker of clinical benefit.

No significant financial relationships to disclose.