Original PaperCisplatin (P), vinblastine (V) and bleomycin (B) combination chemotherapy in recurrent or advanced granulosa(-theca) cell tumours of the ovary. An EORTC gynaecological cancer cooperative group study
Introduction
granulosa- and theca-cell tumours are rare functional sex cord-stromal ovarian tumours. As a group they comprise only 2–3% of all ovarian malignancies. Pure thecomas are regarded as benign tumours but pure or mixed granulosa cell tumours (GCTs) should all be regarded as potentially malignant, although recurrence and metastasis may be slow 1, 2, 3, 4. In their review of 305 patients with granulosa- and theca-cell tumours, Björkholm and Pettersson [4] reported that none of the thecoma patients died but that 21% of those with GCT died from their disease.
The majority of GCTs present as FIGO stage I as the hormonal symptoms make an early diagnosis possible 2, 3. When surgically treated the 5-year survival rate for stage I is 90%, but patients with advanced disease have a 5-year survival ranging from 0 to 22% 4, 5, 6.
In the majority of cases, the initial form of therapy is surgery [5]. The selection of patients for any postoperative treatment is controversial [7]. In patients with advanced disease, postoperative chemo-, or hormono- or radiotherapy should be considered. In those patients with recurrent or metastatic disease, therapy has not yet been standardised 5, 7.
Over the past decade, platinum-based combination chemotherapy has emerged as the most widely used postoperative treatment in GCTs. Although a number of responses have been reported in small series or case reports, the highest identified response rates were obtained with the PVB regimen (cisplatin, vinblastine and bleomycin), but toxicity was significant [7].
The European Organization for Research and Treatment of Cancer (EORTC) Gynaecological Cancer Co-operative Group initiated a prospective clinical trial to investigate the clinical activity of a modified PVB regimen and its additional toxicity in patients with poor prognosis GCTs. Adjustment of the regimen was achieved by reducing the cumulative doses of vinblastine and bleomycin per cycle and increasing the interval between successive cycles by a week compared with the original reported PVB 8, 9. The early results have been published in abstract form [10].
Section snippets
Patients and methods
38 patients with advanced or recurrent GCT of the ovary were entered into a prospective clinical trial conducted by the Gynaecological Cancer Co-operative Group of the European Organization for Research and Treatment of Cancer (EORTC/GCCG). All patients were treated with PVB combination chemotherapy. The dosage and schedule of administration of chemotherapy consisted of: cisplatin (P), 20 mg/m2 on days 1–5 by intravenous (i.v.) infusion over a 3-h period with (pre)hydration with normal saline;
Results
From December 1984 to June 1991, 53 patients were registered in the trial. Follow-up was not sufficient in 4 patients. 10 other patients were considered ineligible, 4 with incorrect histological diagnosis (adenocarcinoma 1, lymphoma 1, small cell carcinoma of the ovary 2) and 6 with ineligible staging (FIGO stage IIb 3, no measurable lesions 3). One eligible patient did not receive any treatment. During the premedication for cisplatin she suffered a pulmonary embolism and consequently
Discussion
The literature concerning the use of postoperative chemotherapy in advanced or recurrent GCTs consists mainly of some small series of case reports. Initially objective responses were reported with alkylating agents 12, 13, 14, 15, 16. Thereafter reports appeared on the use of doxorubicin [17], doxorubicin/bleomycin [18] and actinomycin/5-fluorouracil/cyclo-phosphamide 16, 19. These and other available reports suggested that GCTs were indeed responsive to single-agent and combination
Acknowledgements
Other contributors to the study were: P.G. Harper (London), C. Mangioni (Monza), C.F. de Oliveira, Coimbra; W. ten Bokkel-Huinink, Amsterdam; P.J.M. Bakker, Amsterdam; A. Kobierska, Gdansk; P. Zola, Torino; W.P.M. Breed, Eindhoven; M.E.L. van der Burg, Rotterdam; J.P. Neijt, Utrecht; K.J. Roozendaal, Amsterdam; A.T. van Oosterom, Leiden; J.E.G.M. Stoot, Heerlen; P.H.B. Willemse, Groningen; E. Ploch, Warsaw; C. Belloni, Milano. This publication was supported by a grant from the Dutch Cancer
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