Gemcitabine and carboplatin

Fatal cholestatic hver failure occurred in a 45-year-old woman with metastatic breast cancer who was given gemcitabine and carboplatin and pre-existing liver damage. After four courses of gemcitabine -I- carboplatin she developed severe decompensated cholestatic hepatitis (9). Liver biopsy showed marked cholestasis and hepatocellular injury consistent with drug-induced hepatotoxicity. 

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. 

Studies in mice bearing the OCa-1 ovarian cancer demonstrated that CT-2103 is synergistic when co-administered with gemcitabine, doxombicin, irinotecan, and carboplatin in a schedule independent manner (data not shown). Preliminary data indicate that it is also a substantially more potent radiosensitiser than pachtaxel in Cremophor EL/ethanol with an... 

Combination studies of olaparib are being explored clinically with a number of agents, including irinotecan, dacarbazine, carboplatin, gemcitabine, doxorubicin, cisplatin, and topotecan. 

Chemotherapeutic agents that have significant cancer response when combined with hyperthermia (up to 43°C) include doxorubicin, melphalan, mitomycin C (MMC), mitoxantrone, gemcitabine, etoposide, and especially the platinum-based agents carboplatin and oxaliplatin (Mohamed et al., 2003 Sugarbaker et al., 2005). Agents that do not work well with hyperthermia include irinotecan, paclitaxel, docetaxel, 5-fluorouracil, and floxuridine (Mohamed et al., 2003 Sugarbaker et al., 2005). 

We observed longer survival and a trend toward improved response in gemcitabine/ cisplatin-treated stage IV NSCLC patients with low ERCCl mRNA levels (31). A higher response rate was observed in locally advanced NSCLC patients with low levels of ribonucleotide reductase subunit Ml (RRMl) and ERCCl treated with induction gemc-itabine/carboplatin (32). ERCCl protein expression by immunostaining was associated with survival in NSCLC patients treated with cisplatin-based adjuvant therapy (33). 

The possible impact of co-administered chemotherapies and radiation therapy on the PK of cetuximab was furthermore assessed using the population PK approach, as described in Section 14.6. The co-administered chemotherapies included cisplatin, carboplatin, paclitaxel, doxorubicin, irinotecan, and gemcitabine. The results of the analysis indicate that neither the co-administered chemotherapies nor radiation therapy had a significant impact on the PK of cetuximab. This finding suggests that the potential for PK-based drug-drug interactions with cetuximab is low. 

Newer platinum-based combinations have proven effective in Phase-II studies of patients with advanced disease. Carboplatin/paclitaxel (response rate 23%) and cisplatin/gemcitabine (response rate 24%) have figured prominently [142] [143], The carboplatin/paclitaxel combination appears remarkably active in the induction setting, as Dang et al. reported response rates of 95% [144], and also when given weekly with concurrent radiotherapy... 

A number of cytotoxic agents have demonstrated significant singleagent activity in chemotherapy-naive patients with limited- and extensive-disease SCLC, but the activity in recurrent or refractory SCLC is modest. Among the more commonly used chemotherapy agents in the United States are cisplatin, carboplatin, etoposide (intravenous and oral regimens), topotecan, paclitaxel, docetaxel, and gemcitabine. 

Kelly K, Mikhaeel-Kamel N, Pan Z, et al. A phase I/II trial of paclitaxel, carboplatin, and gemcitabine in untreated patients with advanced nonsmall cell lung cancer. Clin Cancer Res 2000 6 3474-3479. 

Hansen SW, Anderson H, Boman K, et al. Gemcitabine, carboplatin and paclitaxel (GCP) as first-line treatment of ovarian cancer FIGO stages IIB-FV. Proc Am Soc Clin Oncol 1999 18 357a (Abstract). 

Joyce, a psychologist. Ovarian cancer, stage 3, diagnosed in 2004 at age fifty-eight. (Treatment surgery, hysterectomy, splenectomy, and colon resection. Chemo carboplatin, paclitaxel, cisplatin, gemcitabine, topotecan, doxorubicin.)... 

A number of case reports describe an increase in the effects of warfarin, accompanied by bleeding in some cases, caused by an-tineoplastic regimens containing carboplatin, chlormethine, cyclophosphamide, doxorubicin, etoposide, gefitinib, gemcitabine, ifosfamide with mesna, methotrexate, procarbazine, trastuzum-ab, vincristine or vindesine. A decrease in the effects of warfarin has been seen with azathioprine, cyclophosphamide, mercaptop-urine and mitotane, a decrease in the effects of acenocoumarol has been seen with mercaptopurine, and a decrease in the effects of phenprocoumon have l n seen with azathioprine. 

Wang, H., Li, M., Rinehart, J.J., Zhang, R. (2004). Dexamethasone as a chemoprotectant in cancer chemotherapy hematoprotective effects and altered pharmacokinetics and tissue distribution of carboplatin and gemcitabine. Cancer Chemother. Pharmacol, 53(6), 459-467. 

Helbekkmo N, Sundstrom S, Aasebo U, et al (2007) Vinore-Ibine/carboplatin versus gemcitabine/carboplatin in advanced NSCLC shows similar efficacy, but different impact of toxicity. Br J Cancer 97 283-289 Hennequin C, Giocanti N, Favaudon V (1996) Interaction of ionizing radiation with paclitaxel (Taxol) and doc-etaxel (Taxotere) in HeLa and SQ20B cells. Cancer Res 56 1842-1850... 

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