Phase I Study of High-Dose Epirubicin in Platinum-Pretreated Patients with Ovarian Carcinoma

Vermorken, Jan B.; Huinink, W.W. ten Bokkel; Kobierska, A; Burg, M.E.L. van der; Forni, M; Piccart, Martine; Putten, E. Van Der

doi:10.1159/000011994

Cited by 14 publications

(11 citation statements)

References 22 publications

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“…Anthracyclines play an important role in the management of advanced gynecological malignancies as part of firstline therapy or as salvage therapy. The results of the several clinical trials evaluating doxorubicin and epirubicin in recurrent ovarian, cervical, and endometrial cancers have shown significant response rate (2)(3)(4)(5)(6)(7)(8)(9)(10) . Repeated treatment is limited by the development of cumulative dose-related cardiomyopathy.…”

Section: Discussionmentioning

confidence: 99%

Liposome-encapsulated doxorubicin citrate in previously treated recurrent/metastatic gynecological malignancies

Angioli

Palaia

Calcagno

et al. 2007

International Journal of Gynecological Cancer

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The aim of this study was to evaluate the safety and efficacy of liposome-encapsulated doxorubicin citrate (LEDC) in patients affected by recurrent/metastatic gynecological malignancies scheduled for palliative chemotherapy. Inclusion criteria were proven recurrent/advanced gynecological neoplasms, measurable/assessable disease, adequate organ function, left ventricular ejection fraction >50% as determined by echocardiography, informed consent. LEDC was administered intravenously over 1 h at the dose of either 75 mg/m(2) or 60 mg/m(2) (every 3 weeks until disease progression or toxicity prohibiting further therapy). From May 2003 to September 2005, 36 patients were enrolled. Primary disease was ovarian, endometrial, and cervical cancers in 15 (42%), 11 (30%), and 10 (28%) patients, respectively. LEDC was employed as third- or fourth-line chemotherapy in 25 (70%) and 11 (30%) patients, respectively. The median number of courses of LEDC received was 3 (range 2-9). Six patients (17%) achieved a partial response to treatment lasting 27 weeks and 10 patients (28%) experienced stable disease lasting 18 weeks. The predominant toxicity was hematological, especially neutropenia. Among patients receiving a dose of 75 mg/m(2), two (11%) suspended therapy for febrile neutropenia, and nine (50%) required a dose reduction of 25%. As a result, the next 18 patients were treated at a reduced dose (60 mg/m(2)) of LEDC. Severe neutropenia (G3-G4) was significantly less common in this group (61% versus 22%; P= 0.04). LEDC has shown antineoplastic activity in previously treated recurrent/metastatic gynecological cancer patients and the toxicity profile could be considered acceptable at a 60 mg/m(2) dosage.

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Section: Discussionmentioning

confidence: 99%

Liposome-encapsulated doxorubicin citrate in previously treated recurrent/metastatic gynecological malignancies

Angioli

Palaia

Calcagno

et al. 2007

International Journal of Gynecological Cancer

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“…In the series of Markman et al (19) , the response rate to second‐line cisplatin/carboplatin ranged from 27% for patients with a cisplatin‐free interval of 5–12 months to 59% for those with an interval longer than 24 months. Patients with platinum‐sensitive disease have a good chance to respond to platinum retreatment, whereas in platinum‐resistant patients, different agents produce short‐lived response rates up to approximately 30% (Table 1) (22–45) .…”

Section: Second‐line Treatmentmentioning

confidence: 99%

Second-line treatment and consolidation therapies in advanced ovarian cancer

Conte¹,

Gadducci²,

Cianci³

2001

Int J Gynecol Cancer

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Cytoreductive surgery followed by platinum-and paclitaxel-based chemotherapy represents the standard therapeutic strategy for advanced ovarian cancer (1,2) . Current regimens are able to achieve a clinical complete response in 40-50% and a pathologic complete response only in 25-30% of cases, and moreover, about half of complete responders will subsequently develop recurrent disease. On the basis of these data, there is a major interest to assess the role of consolidation therapies after first-line chemotherapy. On the other hands, more than 80% of patients with advanced ovarian cancer need a second-line treatment for persistent/recurrent disease. Consolidation therapySeveral therapeutic tools have been investigated as consolidation treatments in patients who have obtained a complete or partial response after first-line chemotherapy, but currently available results are contrasting (Table 1).In the experience of the Gruppo Oncologico Nord-Ovest (GONO) (3) including patients in complete response or with minimal residual disease at secondlook, consolidation chemotherapy with induction regimen was associated with a better progression-free survival and overall survival when compared to external radiotherapy.Conversely, Lawton et al. (4) reported that both single-agent chlorambucil and whole abdominal radiotherapy gave unsatisfactory results as consolidation treatment after second-look in patients who were given a cisplatin-based regimen. In the study of Sorbe et al. (5) , 98 patients with stage III ovarian cancer in pathological complete response were randomized to receive whole abdomen radiotherapy vs. six further cycles of induction chemotherapy (cisplatin plus doxorubicin or epirubicin) vs. no consolidation treatment. Progression-free survival was better in radio-therapy arm when compared to both chemotherapy arm (P = 0.048) and control arm (P = 0.039), whereas 5-year overall survival was not significantly different in the three groups. The same authors found that, among 74 patients with microscopic residual disease at second-look, consolidation treatment with either whole abdomen irradiation or chemotherapy obtained similar progression-free and overall survival rates.In a retrospective study including 95 patients with FIGO stage IIB-IV ovarian cancer who achieved pathologic complete response, Favalli et al. (6) found that median survival was better in the 43 patients who received consolidation treatment (consisting in chemotherapy in 35 cases) when compared to the 52 patients who did not (66 months vs. 50 months, P = 0.001).Fiorentino et al. (7) randomly allocated 122 pathologically complete responders to receive further chemotherapy with 5-fluorouracil plus cisplatin vs. no consolidation after second-look.Five-year disease free survival (52% vs. 56%) and 5-year overall survival (70% vs. 63%) were similar in the two groups.Intraperitoneal chemotherapy has a strong pharmacologic and biologic rationale in the therapeutic strategy of ovarian cancer, even if these treatment modalities should be still considered as inv...

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“…highdose chemotherapy with peripheral stem cell support or intraperitoneal chemotherapy A third or fourth non-cross-resistant drug can be added to platinum-paclitaxel in form of 3-drug combinations or drugs can be administered sequentially. Several drugs have shown activity against platinum-pretreated ovarian cancer making them candidates for combination with platinum-paclitaxel: anthracylines (epirubicin [62], liposomal doxorubicin [63]), topoisomerase inhibitors (etoposid [64], topotecan [65]), antimetabolites (gemcitabine [66]), vinca alkaloides (vinorelbine [67]), and alkylating agents (treosulfan [68]). Based on the results of the above-mentioned meta-analyses about the role of anthracyclines in ovarian cancer on the one hand and taking into account the published data showing combinations of anthracyclines with both platinum [69] and paclitaxel [70] being feasible on the other hand, the AGO Studiengruppe Ovarialkarzinom started a phase I/II program to evaluate the 3-drug combination of epirubicin-paclitaxel-carboplatin (ET-Carbo).…”

Section: Future Aspectsmentioning

confidence: 99%

First-Line Chemotherapy in Advanced Ovarian Cancer: State of the Art and Future Aspects

Bois¹,

Lück²,

Bauknecht³

1999

Oncol Res Treat

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Over the last 25 years, the principles of treatment for advanced ovarian cancer have not changed. They still consist of primary debulking surgery followed by chemotherapy. Progress in operative and perioperative medicine as well as development of more effective chemotherapies have substantially improved the outcome in these patients. Cornerstones in the development of effective chemotherapies were the introduction of cisplatin in the late 70s and the introduction of paclitaxel in the 90s. Actual standard treatment consisting of a platinum-paclitaxel combination chemotherapy achieves an objective response rate in about 3/4 of patients. Ongoing studies evaluate 3 options to improve efficacy of first-line treatment: (a) incorporation of further non-cross-resistant drugs into first-line regimens; (b) modification of the sequence of treatment modalities; (c) modifications of dose intensity with either intraperitoneal therapy or high-dose chemotherapy with peripheral stem cell support. Future studies will have to focus on how to maintain the high remission rates achieved with primary therapy and translate them into long-term survival.

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Phase I Study of High-Dose Epirubicin in Platinum-Pretreated Patients with Ovarian Carcinoma

Cited by 14 publications

References 22 publications

Liposome-encapsulated doxorubicin citrate in previously treated recurrent/metastatic gynecological malignancies

Liposome-encapsulated doxorubicin citrate in previously treated recurrent/metastatic gynecological malignancies

Second-line treatment and consolidation therapies in advanced ovarian cancer

First-Line Chemotherapy in Advanced Ovarian Cancer: State of the Art and Future Aspects

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