Severe pulmonary toxicity in patients treated with a combination of docetaxel and gemcitabine for metastatic transitional cell carcinoma

Dunsford, M. L.; Mead, G. M.; Bateman, A C; Cook, Theresa A.; Tung, Kaity

doi:10.1023/a:1008377819875

Cited by 80 publications

(52 citation statements)

References 21 publications

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“…Published literature reports describe apparently similar presentations of gemcitabine-associated lung injury with the terms capillary leak syndrome, 24,26 -30 noncardiogenic pulmonary edema, 16,31,32 interstitial pneumonitis, 16,[33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48] acute pneumonitis, 49 acute respiratory distress syndrome, 8,36,50,51 acute pulmonary toxicity, 52 or acute lung injury. 16,44,45,36,46,[53][54][55][56] In conclusion, our findings highlight the importance of consideration of the risk of lung injury from drug-drug or drug-radiotherapy interactions in designing novel therapeutic regimens for cancer patients, particularly for drugs with additive or synergistic pulmonary toxicity. The MedWatch program is the mechanism by which healthcare professionals …”

Section: Discussionmentioning

confidence: 71%

Clinical features and correlates of gemcitabine‐associated lung injury

Belknap

Kuzel

Yarnold

et al. 2006

Cancer

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BACKGROUNDGemcitabine is a commonly used chemotherapeutic agent structurally and pharmacologically similar to cytarabine. Recently, instances of severe gemcitabine‐associated lung injury have been reported. Herein, investigators affiliated with the Research on Adverse Drug Events and Reports (RADAR) pharmacovigilance program evaluated clinical characteristics of gemcitabine‐associated severe acute lung injury from clinical trial reports, medical literature case reports, and spontaneous reports to the Food and Drug Administration (FDA) Adverse Event Reporting System (AERS).METHODSClinical data were obtained by reviewing adverse event case reports for gemcitabine‐associated lung injury as reported in the medical literature and in the FDA AERS database. Upper limit estimates of ADE rate were derived from review of published clinical trials reporting gemcitabine‐associated lung injury rates of 10% or higher.RESULTSA total of 178 reports of gencitabine‐associated lung injury were identified; in AERS, there were 55 cases from clinical trials and 92 spontaneous reports. A comprehensive search revealed 31 medical literature reports. Clinical features of gemcitabine‐associated lung injury included dyspnea, fever, pulmonary infiltrate, and cough with recognition of toxicity occurring after a median duration of 48 (range, 1‐529) days after initiation of gemcitabine. The taxanes, docetaxel and paclitaxel, were frequently reported as coadministered therapies. Eleven Phase II or Phase III clinical trials with 317 patients identified gemcitabine‐associated lung injury rates of greater than 10%, with the highest rates (22% and 42%) being observed in Phase III clinical trials where Hodgkin disease patients were treated with a regimen that included gemcitabine and bleomycin.CONCLUSIONSHigh rates of gemcitabine‐associated severe lung injury were observed when gemcitabine was combined with other therapies known to also cause lung injury. Physicians should have a high index of suspicion for this toxicity and report the relevant clinical findings to the FDA's AERS. Cancer 2006. © 2006 American Cancer Society.

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Section: Discussionmentioning

confidence: 71%

Clinical features and correlates of gemcitabine‐associated lung injury

Belknap

Kuzel

Yarnold

et al. 2006

Cancer

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“…Several studies have reported the development of severe pulmonary toxicity in association with gemcitabine. The incidence of pulmonary toxicity has been estimated to vary from 0 to 5% (Roychowdhury et al, 2002;Barlesi et al, 2003) and may be increased by administering bleomycin (Friedberg et al, 2003;Bredenfeld et al, 2004) or docetaxel (Dunsford et al, 1999;Kouroussis et al, 2004) in combination with gemcitabine. In the above-mentioned study by Bredenfeld et al, gemcitabine was given on days 1 and 4 of each Gemcitabine and cisplatin in lymphoma M Ng et al 3 weekly cycle and the dose was increased from 800 to 1500 mg m À2 .…”

Section: Discussionmentioning

confidence: 99%

Gemcitabine, cisplatin and methylprednisolone (GEM-P) is an effective salvage regimen in patients with relapsed and refractory lymphoma

Waters

Cunningham

et al. 2005

Br J Cancer

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There is currently no standard salvage chemotherapy regimen in relapsed and refractory lymphoma. Gemcitabine is a novel nucleoside analogue, which acts synergistically with cisplatin both in vitro and in clinical studies. We evaluated the combination of gemcitabine, cisplatin and methylprednisolone (GEM-P) in 41 heavily pretreated patients with relapsed and refractory Hodgkin's and non-Hodgkin's lymphoma. The best-achieved response rate (RR) was 79% (95% CI 64 -91), with a complete RR of 21%. In patients with chemo-resistant disease, the RR was 63%. Myelosuppression was the main toxicity, the incidence of Grade 3 or 4 anaemia, neutropenia and thrombocytopenia was 17.1, 61.0 and 53.7% respectively. Only one patient had neutropenic sepsis and none of the patients suffered from haemorrhage. Grade 3 or 4 nonhaematological toxicity was minimal and stem cell mobilisation was not inhibited. GEM-P is an effective salvage regimen and its use prior to autologous stem cell transplant warrants further investigation.

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“…Pulmonary toxicity and refractory peripheral edema are the most common severe adverse events worth noting [42,43]. Thrombocytopenia and neutropenia are common, even with the use of growth factor support [41].…”

Section: Gemcitabine and Docetaxel: Clinical Studies (Table 2)mentioning

confidence: 99%

Gemcitabine and Docetaxel in Metastatic Sarcoma: Past, Present, and Future

Maki

2007

The Oncologist

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Objective. In the era of oral molecular kinase inhibitors, cytotoxic chemotherapy agents are somewhat overlooked, but remain the backbone of treatment for most cancers. Patients with non-gastrointestinal stromal tumor sarcomas, such as leiomyosarcoma, liposarcoma, and undifferentiated high-grade pleomorphic sarcoma (formerly called malignant fibrous histiocytoma), have received doxorubicin and ifosfamide as the backbone of their treatment for over 15 years or more. The goal of this article is to review the data that have led to the use of gemcitabine and docetaxel as a useful combination for patients with metastatic sarcomas, and to comment on possible synergy of the combination.Methods and results. The literature regarding the use of gemcitabine, docetaxel, or both, is reviewed, with emphasis on patients with metastatic sarcoma.Results. Activity of gemcitabine and docetaxel is observed in leiomyosarcoma and undifferentiated highgrade pleomorphic sarcoma. There is apparent schedule dependence of the combination in other cancers; it is unclear if schedule matters in patients with sarcomas. The dose and schedule of gemcitabine and docetaxel examined in phase II studies are probably too high for routine practice.Conclusions. The combination of gemcitabine and docetaxel is an effective option for patients with metastatic sarcoma, increasing the armamentarium for the practicing oncologist in treating this heterogeneous group of diseases. Given the low response rate to docetaxel as a single agent, it is likely that there is true clinical synergy of the combination. The Oncologist 2007;12: 999 -1006 Disclosure of potential conflicts of interest is found at the end of this article.

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Severe pulmonary toxicity in patients treated with a combination of docetaxel and gemcitabine for metastatic transitional cell carcinoma

Cited by 80 publications

References 21 publications

Clinical features and correlates of gemcitabine‐associated lung injury

Clinical features and correlates of gemcitabine‐associated lung injury

Gemcitabine, cisplatin and methylprednisolone (GEM-P) is an effective salvage regimen in patients with relapsed and refractory lymphoma

Gemcitabine and Docetaxel in Metastatic Sarcoma: Past, Present, and Future

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