A phase I study of gemcitabine and epirubicin for the treatment of platinum-resistant or refractory advanced ovarian cancer

Pignata, Sandro; Varriale, Elisa; Casella, G.; Iodice, F.; Placido, Giuseppe De; Perrone, Francesco; Tramontana, Flavia; Ricchi, Paolo; DeVivo, R.; Costanzo, Raffaele; Vernaglia, Alessandra; Tramontana, S.

doi:10.1023/a:1008344528791

Cited by 11 publications

(7 citation statements)

References 18 publications

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“…It has been quickly elucidated that clinical symptoms moderately improved, but there was no real tumor-associated response. Subsequently, study groups focused their interest on reasonable combination therapy regimens with the well-tolerated gemcitabine [16][17][18][19][20][21][22][23][24][25][26]. The majority of study groups immediately performed phase II trials using fixed combination therapies, based on their experiences, and reported on response rates and survival.…”

Section: Discussionmentioning

confidence: 99%

“…Results of 31 phase I trials published between 1999 and 2000 have shown that it is essential to find the optimal dosage for combination therapy with other cytostatic drugs [12][13][14][15]. In various tumor types, gemcitabine has been combined with epirubicin [16][17][18], vinorelbine [19][20][21], oral uracil-tegafur [22] and multitargeted antifolate [23,24], for which well-tolerable combination chemotherapy protocols have been generated, but these regimens have not become relevant for pancreatic carcinoma.…”

Section: Discussionmentioning

confidence: 99%

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Phase I Trial Using Weekly Administration of Gemcitabine and Docetaxel in Patients with Advanced Pancreatic Carcinoma

Meyer¹,

Lueck²,

Hribaschek³

et al. 2004

Chemotherapy

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Background: In advanced pancreatic carcinoma, no effective chemotherapy has been found yet due to the lack of appropriate response. The frequent use of gemcitabine is based on the fact that there is a significant improvement in the quality of life, but neither an effect on remission nor a detectable increase in survival rates could be observed. Therefore, the hypothesis was that the combination of gemcitabine with other drugs can result in a better outcome of patients. The aim of this study was to determine the maximally tolerable dosage of gemcitabine and docetaxel using a weekly administration regimen. Patients and Methods: Twenty-five patients with advanced or metastatic pancreatic carcinoma received combination chemotherapy using gemcitabine and docetaxel in a weekly administration regimen, beginning with 800 mg/m² of gemcitabine and 25 mg/m² of docetaxel. Four patients were originally enrolled for each of the seven different dosages of both drugs. Side effects were assessed according to the WHO standard. Quality of life was evaluated according to the Core Quality of Life Questionnaire (QLQ-C30) of the European Organization for Research and Treatment of Cancer. Results: Using the two maximal dosages of gemcitabine and docetaxel (gemcitabine, 800 and 1,000 mg/m², and docetaxel, 45 and 40 mg/m²; respectively), only 3 and 2 patients were enrolled, respectively, because of toxic side effects ≧ grade III according to WHO grading. Maximal dosages with tolerable side effects were 1,000 mg/m² of gemcitabine and 35 mg/m² of docetaxel given in weekly intervals. Main side effects of this combination chemotherapy were gastrointestinal symptoms and hematologic toxicity. Conclusion: Combination therapy with gemcitabine and docetaxel in advanced or metastatic pancreatic carcinoma is a well-tolerated and acceptable alternative treatment option with regard to the severity of side effects and its positive impact on quality of life and tumor-associated pain. According to the study endpoint, dosages of 1,000 mg/m² of gemcitabine and 35 mg/m² of docetaxel are recommended as maximum-tolerated doses (given in weekly intervals) for a future phase II trial.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Phase I Trial Using Weekly Administration of Gemcitabine and Docetaxel in Patients with Advanced Pancreatic Carcinoma

Meyer¹,

Lueck²,

Hribaschek³

et al. 2004

Chemotherapy

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“…In addition, gemcitabine has been combined in various tumor entities with epirubicin [16,50,69], vinorelbine [15,18,34], oral UFT [49], and the antifolate MTA [1,2], using well-tolerable protocols, but probably with no relevance for pancreatic carcinoma.…”

Section: Chemotherapymentioning

confidence: 99%

Current Options for Palliative Treatment in Patients with Pancreatic Cancer

Ridwelski

Meyer²

2001

Dig Dis

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Palliative treatment is often the only remaining option in the management of pancreatic carcinoma, but its efficacy is poor due to low tumor sensitivity and inadequate treatment protocols. There are several options of palliative treatment with antitumor or supportive intention. Classical end points of palliative treatment are survival, tumor response, and quality of life. A decade ago, palliative chemotherapy consisted mainly of 5-fluorouracil as the standard agent in combination with either other agents and/or radiotherapy. Only the new antineoplastic drug gemcitabine, which was introduced simultaneously with the definition of novel end points of chemotherapy such as clinical benefit, allowed to achieve some progress. However, while gemcitabine monotherapy appeared to be superior to 5-fluorouracil and improved important parameters of quality of life, it could not provide a significant improvement of survival. A novel concept, therefore, is to improve this beneficial cytostatic response in pancreatic carcinoma using a gemcitabine-based protocol by combining it with antineoplastic drugs such as taxanes or platin analogs. This strategy may have the potential to improve the outcome in palliative chemotherapy of pancreatic carcinoma patients with advanced tumor growth or metastases. Best supportive care in pancreatic cancer consists of the treatment of symptoms, such as pain, jaundice, duodenal obstruction, weight loss, exocrine pancreatic insufficiency, and tumor-associated depression.

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“…Several studies using GEM as a single agent in cisplatin-resistant patients have been performed with response rates of approximately 20% and well-tolerated hematological and non-hematological toxicity [8, 9, 10]. Given its mechanisms of action and favorable toxicity profile, combinations of GEM with other drugs (cisplatin, taxol, epirubicin or topotecan) have been explored in preclinical as well as clinical trials [11, 12, 13, 14]. In particular, a synergistic cytotoxic effect has been observed in human breast cancer cell lines when GEM was administered after doxorubicin [15].…”

Section: Introductionmentioning

confidence: 99%

Phase I Study of Gemcitabine and Liposomal Doxorubicin in Relapsed Ovarian Cancer

et al. 2002

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Twenty-three patients were enrolled in a phase I study conducted to determine the maximum tolerated doses (MTD) of combined liposomal doxorubicin (CAE) and gemcitabine (GEM) in relapsed ovarian cancer patients. A total of 82 courses are evaluable, with a median number of three cycles administered per patient (range 2–8). GEM was administered on days 1 and 8 by 30-min intravenous infusion immediately after CAE given by 60-min intravenous infusion on day 1; cycles were repeated every 21 days. The starting doses were CAE 20 mg/m² and GEM 600 mg/m². Following dose levels were 20/800; 20/1,000; 30/800; 30/1,000; 35/800, and 35/1,000 for CAE and GEM, respectively. The MTD was reached at dose level 5, with febrile neutropenia and thrombocytopenia as dose-limiting toxicities. After the MTD, granulocyte-colony stimulating factor was administered in 15% of cycles. Non-hematological toxicity was mild and manageable. All patients are so far evaluable for response. Among them, 5 partial responses (21.7%; 95% confidence interval, CI: 4.9–38.5), 5 disease stabilizations (21.7%, 95% CI: 4.9–38.5) and 13 progressions (56.6%, 95% CI: 36.4–76.8) have been registered. These results warrant further research in a phase II study.

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A phase I study of gemcitabine and epirubicin for the treatment of platinum-resistant or refractory advanced ovarian cancer

Abstract: The combination of gemcitabine 1000 mg/m2 (day 1, 8) and epirubicin at 60 mg/m2 (day 1) is a feasible therapy. Grade 4 neutropenia is frequent and G-CSF support is often required. With prophylactic support of G-CSF, the DLT is thrombocytopenia.

Cited by 11 publications

References 18 publications

Phase I Trial Using Weekly Administration of Gemcitabine and Docetaxel in Patients with Advanced Pancreatic Carcinoma

Phase I Trial Using Weekly Administration of Gemcitabine and Docetaxel in Patients with Advanced Pancreatic Carcinoma

Current Options for Palliative Treatment in Patients with Pancreatic Cancer

Phase I Study of Gemcitabine and Liposomal Doxorubicin in Relapsed Ovarian Cancer

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