Gemcitabine toxicity

Monks A, Harris E, Connelly J, et al. Enhancement of fludarabine and gemcitabine toxicity by UCN-01 in a variety of human tumor cell lines. Proc Am Assoc Cancer Res 1999 40 Abstract 45. 

Gemcitabine Gemcitabine 1250 mg/M2 IV (over 30 min) days 1,8,15 -20% dose increase permitted if no toxicity after first 4 week cycle... 

Four to six cycles of doublet chemotherapy with cisplatin or carboplatin plus docetaxel, gemcitabine, paclitaxel, or vinorelbine are recommended as first-line chemotherapy for patients with unresectable stage III or IV NSCLC. No combination was found to be superior tolerance of expected toxicities may contribute to the decision. 

In our review of the available data, concurrent gemcitabine and radiation possesses high activity in the treatment of advanced cancers of the head and neck. Unfortunately, the toxicity of this combination also appears to be significant. Strategies to reduce toxicity are needed in future clinical trials evaluating this combination. 

Pavlakis N, Bell DR, Millward MJ, et al. Fatal pulmonary toxicity resulting from treatment with gemcitabine. Cancer 1997 80(2) 286-291. 

Gemcitabine (Gemzar), an antimetabolite, undergoes metabolic activation to difluorodeoxycytidine triphosphate, which interferes with DNA synthesis and repair, ft is the single most active agent for the treatment of metastatic pancreatic cancer, and it is used as a first-line treatment for both pancreatic and small cell lung cancer. It is administered by intravenous infusion. The dose-limiting toxicity is bone marrow suppression. 

Gemcitabine was initially approved for use in pancreatic cancer but is now widely used in the treatment of non-small cell lung cancer and bladder cancer. Myelosuppression is the principal dose-limiting toxicity. 

Adverse effects Myelosuppression is the dose-limiting toxicity of gemcitabine. Other toxicities are nausea, vomiting, alopecia, and rash. Transient elevations of serum transaminases, proteinuria, and hematuria are common. Resistance to the drug is probably due to its inability to be converted to a nucleotide the tumor cell produces increased levels of endogenous deoxycytidine that compete for the kinase, thereby by-passing the inhibition. 

IPC proved valnable for estimating peptide hydrophobicity [13]. Pharmaceutical science utilized IPC to monitor rat serum esterase activities [14] and also to analyze relationship between plasma concentrations at the end of infusion and toxicity profiles of fixed-dose-rate gemcitabine plus carboplatin [15]. An IPC trap was also used in an online desalting-mass spectrometry system. This system allows ionic compounds in a nonvolatile buffer to be introduced into a MS for strutural elucidation. The trap column was equilibrated with a volatile IPR, the target analyte and the nonvolatile buffer ions (phosphate and sodium ions) were transferred into the trap column, but only the target analyte that interacts with the volative IPR can be retained phospahte buffer ion were eluted from the trap column and the target analyte was eluted by oragnic solvent in a backflush mode and introduced into the MS. 

Wang, L.R. et al. The efficacy and relationship between peak concentration and toxicity profile of fixed-dose-rate gemcitabine plus carboplatin in patients with advanced non-small-cell lung cancer. Cancer Chemother. Pharm. 2007, 60, 211-218. 

Gemcitabine can cause pulmonary toxicity. The clinical presentation is subacute and often non-specific. Chest X-ray usually shows reticulonodular interstitial infiltrates (5). 

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