Gemcitabine Pulmonary Toxicity in Ovarian Cancer

Ko, Emily; Lee, Susanna; Goodman, Annekathryn

doi:10.1634/theoncologist.2008-0049

Cited by 15 publications

(21 citation statements)

References 12 publications

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“…There are several reports of pulmonary toxicity due to usage of gemcitabine as a single agent (Pavlakis et al 1997;Galvão et al 2010;Vahid and Marik 2008;Belknap et al 2006;Ko et al 2008;Shaib et al 2008) or in combination with other anti-neoplastic agents (Takeda et al 2009;Esteban et al 2008;Boeck et al 2007;Czarnecki and Voss 2006). In the present study, we found a relatively high incidence of ILD (7.6%) in patients treated with gemcitabine compared to previous reports (Ohe et al 2007;Crinò et al 1999;Burris et al 1997;Briasoulis and Pavlidis 2001;Roychowdhury et al 2002).…”

Section: Discussionsupporting

confidence: 45%

Interstitial lung disease associated with gemcitabine treatment in patients with non-small-cell lung cancer and pancreatic cancer

Umemura

Yamane

Suwaki

et al. 2011

J Cancer Res Clin Oncol

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Section: Discussionsupporting

confidence: 45%

Interstitial lung disease associated with gemcitabine treatment in patients with non-small-cell lung cancer and pancreatic cancer

Umemura

Yamane

Suwaki

et al. 2011

J Cancer Res Clin Oncol

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“…They found co-administered therapy rates of toxicity to be 10% to 43% 7. The highest rates were reported to occur in Hodgkin’s patients being treated with concomitant bleomycin therapy (22%–42%) 16–18. Other chemotherapy combinations found to have higher incidence of pulmonary toxicity included gemcitabine plus vinorelbine, paclitaxel, or docetaxel, each of which is known to induce cytokine release, leading to increased inflammation and cumulative pulmonary toxicity 7…”

Section: Discussionmentioning

confidence: 99%

A Case of Late-Onset Gemcitabine Lung Toxicity

Sherrod

Brufsky

Puhalla

2011

Clin Med Insights Oncol

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Gemcitabine is a chemotherapeutic agent used for the treatment of a number of malignancies. Although its major dose-limiting side effect is myelosuppression, many pulmonary toxicities have been described with its use. Severe pulmonary toxicity is rare, but symptoms tend to be rapid in onset and potentially deadly. The average time from initiation of chemotherapy to onset of symptoms is less than two months. The most effective therapy is steroid administration, the efficacy of which has been variable. In this report, we describe a unique case of gemcitabine pulmonary toxicity in a patient who did not experience symptoms of pulmonary dysfunction until after 1 year of treatment. Her symptoms did not improve rapidly with steroids, nor did she rapidly decompensate as has been frequently described. To our knowledge, this is one of the first reported descriptions of late-onset gemcitabine lung toxicity.

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“…[26][27][28] To avoid severe toxicity and improve survival, GMT-based therapy is often used in combination with other agents. 6,[20][21][22][23][24][25][33][34][35][36] We have previously shown that TMX, as a CaM antagonist, induces apoptosis in human cholangiocarcinoma cells, which lack ERs. [10][11][12][13] We reported that TMX-induced apoptosis is partially dependent on inhibition of pAKT and FLIP expression, as well as activation of caspases 8, 10, 9, and 3.…”

Section: Discussionmentioning

confidence: 99%

“…32 Low dose of GMT is preferred to avoid severe toxicity, especially pulmonary toxicity. [33][34][35][36] Hence, combination therapies with GMT plus a variety of chemotherapeutic agents have been employed to minimize toxicity and maximize therapeutic efficacy. Currently, GMT combined with chemicals like leucovorin, 5-fluorouracil, capecitabine, and platinum agents have shown enhanced therapeutic effects in cholangiocarcinoma.…”

mentioning

confidence: 99%

Tamoxifen enhances therapeutic effects of gemcitabine on cholangiocarcinoma tumorigenesis

Yuan

Turk

et al. 2011

Laboratory Investigation

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Cholangiocarcinoma is a highly malignant tumor with limited therapeutic options. We have previously reported that tamoxifen (TMX) induces apoptosis of cholangiocarcinoma cells and reduces cholangiocarcinoma tumorigenesis in mice.In the present studies, we determined the effect of combination therapy of TMX and gemcitabine (GMT), another chemotherapeutical reagent for many cancers, on cholangiocarcinoma tumorigenesis and investigated the responsible mechanisms. GMT inhibited cell growth and induced apoptosis of cholangiocarcinoma cells in a concentrationdependent manner. TMX enhanced GMT-induced apoptosis of cholangiocarcinoma cells. Consistently, GMT (15 mg/kg) inhibited cholangiocarcinoma tumorigenesis in nude mice by 50%. TMX (15 mg/kg) enhanced the inhibitory effect of GMT on tumorigenesis by 33%. The inhibition of tumor growth correlated with enhanced apoptosis in tumor tissues. To elucidate the mechanisms underlying the additive effects of TMX on GMT-induced apoptosis, we determined the activation of caspases in cholangiocarcinoma cells exposed to GMT, TMX, or both. Activation of caspases 9 and 3, as well as cytochrome c release to the cytosol, was demonstrated in cells exposed to both reagents. In contrast, TMX activated caspase 2, whereas GMT had no effect. Inhibition of caspase 2 activation decreased TMX-, but not GMT-, induced activation of caspase 3 and apoptosis of cholangiocarcinoma cells. Similarly, activation of caspase 2 was found in tumors from TMX-treated mice, but not GMT-treated mice. Therefore, the enhanced effect of TMX on GMT-induced cholangiocarcinoma cell death is partially mediated by activation of caspase 2. TMX and GMT both induce apoptosis and inhibit cholangiocarcinoma tumorigenesis, which may be attributed to the activation of distinct apoptosis signals by TMX and GMT. Our studies provide in vivo evidence and molecular insight to support the use of TMX and GMT in combination as an effective therapy for cholangiocarcinoma.

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Gemcitabine Pulmonary Toxicity in Ovarian Cancer

Cited by 15 publications

References 12 publications

Interstitial lung disease associated with gemcitabine treatment in patients with non-small-cell lung cancer and pancreatic cancer

Interstitial lung disease associated with gemcitabine treatment in patients with non-small-cell lung cancer and pancreatic cancer

A Case of Late-Onset Gemcitabine Lung Toxicity

Tamoxifen enhances therapeutic effects of gemcitabine on cholangiocarcinoma tumorigenesis

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