Abstract | BACKGROUND: METHODS: The temsirolimus dose was 25 mg or 37.5 mg i.v. weekly with escalating doses of cixutumumab (3, 5, or 6 mg/kg i.v. weekly). No patients with diabetes or hyperlipidemia at baseline were eligible until the expansion cohort. We assessed metabolic derangements in our patient cohort, their management, and their association with tumor shrinkage, time to progression ( TTP) and overall survival (OS). RESULTS: Of the 57 patients analyzed, hyperglycemia was seen in 36 (63%) (grade 1-2: 33 [58%]; grade 3-4: 3 [5%]). The median blood sugar level (fasting and nonfasting) across cohorts was 149 mg/dL (upper limit of normal: 110 mg/dL). No patient developed diabetic ketoacidosis or nonketotic hyperosmolar coma or pancreatitis during treatment. Median maximum triglyceride, cholesterol, and low-density lipoprotein levels achieved were 247 mg/dL (range: 65-702 mg/dL), 243 mg/dL (range: 103-424 mg/dL), and 153 mg/dL (range 50-375 mg/dL), respectively. Higher glucose levels were associated with more RECIST tumor shrinkage (r = -.30 [95% confidence interval: -.52, -.03; p = .03]). There was no association between metabolic toxicities of the mTOR and IGF-1R combination and TTP or OS. CONCLUSION: IMPLICATIONS FOR PRACTICE: Results of this study show that the combination of temsirolimus and cixutumumab is safe. The most common side effects, hyperglycemia and hyperlipidemia, are tolerable and manageable. This combination of therapies should not be withheld from diabetic patients and patients with high cholesterol levels. Collaboration between oncologist and endocrinologist allows for individualized treatment and better control of these adverse events, with few dose interruptions and reductions. Supportive care and close monitoring is needed. Those patients who develop hyperglycemia or hypercholesterolemia may benefit more from the drug.
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Authors | Naifa L Busaidy, Patricia LoRusso, Kristie Lawhorn, Kenneth R Hess, Mohammed Amir Habra, Siqing Fu, David S Hong, Helen X Chen, Lawrence A Doyle, Razelle Kurzrock, Aung Naing |
Journal | The oncologist
(Oncologist)
Vol. 20
Issue 7
Pg. 737-41
(Jul 2015)
ISSN: 1549-490X [Electronic] England |
PMID | 26054632
(Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)
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Copyright | ©AlphaMed Press. |
Chemical References |
- Antibodies, Monoclonal
- Antibodies, Monoclonal, Humanized
- cixutumumab
- temsirolimus
- MTOR protein, human
- Receptor, IGF Type 1
- TOR Serine-Threonine Kinases
- Sirolimus
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Topics |
- Adolescent
- Adult
- Aged
- Antibodies, Monoclonal
(administration & dosage, adverse effects)
- Antibodies, Monoclonal, Humanized
- Antineoplastic Combined Chemotherapy Protocols
(adverse effects, therapeutic use)
- Female
- Humans
- Hypercholesterolemia
(chemically induced, epidemiology)
- Hyperglycemia
(chemically induced, drug therapy, epidemiology)
- Hyperlipidemias
(chemically induced, epidemiology)
- Male
- Middle Aged
- Neoplasms
(complications, drug therapy, metabolism, pathology)
- Receptor, IGF Type 1
(immunology)
- Sirolimus
(administration & dosage, adverse effects, analogs & derivatives)
- Survival Analysis
- TOR Serine-Threonine Kinases
(antagonists & inhibitors)
- Treatment Outcome
- Young Adult
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