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Vincristine, Cisplatin, Teniposide and Cyclophosphamide Combination in the Treatment of Recurrent or Metastatic Adrenocortical Cancer
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Pathology.
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2004 (English)In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 21, no 2, 167-177 p.Article in journal (Refereed) Published
Abstract [en]

The efficacy and tolerability of a combination of vincristine, cisplatin, teniposide, and cyclophosphamide (OPEC) in 11 patients (median age, 45 yr) with recurrent and/or metastatic adrenocortical cancer (ACC) (seven functional and four nonfunctional) were evaluated. All patients received this regimen after the failure of streptozocin and o,p'-DDD (SO) combination therapy. The regimen comprised cyclophosphamide, 600 mg/m2, and vincristine, 1.5 mg/m2, maximum dose 2.0 mg (d 1); cisplatin, 100 mg/m2 (d 2) and teniposide, 150 mg/m2 (d 4). Cycles were repeated every 4 wk. One to eight cycles (median, six cycles) of OPEC were administered to each patient. The median duration of treatment was 6 mo. The overall 2-yr survival rate was 82% and the median survival since diagnosis was 44 mo while it was 21 mo since start of OPEC therapy. Responses were obtained in nine patients: partial response in two patients, and stable disease in seven patients. The median duration of response was 6.75 mo. A total of 60 cycles of chemotherapy were given to all patients; grade 1-2 toxicity occurred in 57 cycles, while grade 3 toxicity was observed only in two cycles, according to NCI's Common Toxicity Criteria. We conclude that the OPEC regimen may be considered in recurrent or metastatic ACC as a second-line medical treatment. However, the combination is accompanied by considerable side effects and dose modifications are necessary in order to be able to recommend the treatment. This regimen needs further evaluation compared with SO therapy preferably in a randomized multicenter trial.

Place, publisher, year, edition, pages
2004. Vol. 21, no 2, 167-177 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-91695DOI: 10.1385/MO:21:2:167PubMedID: 15299189OAI: oai:DiVA.org:uu-91695DiVA: diva2:164513
Available from: 2004-05-03 Created: 2004-05-03 Last updated: 2017-12-14Bibliographically approved
In thesis
1. New Diagnostic and Therapeutic Approaches in Adrenocortical Cancer
Open this publication in new window or tab >>New Diagnostic and Therapeutic Approaches in Adrenocortical Cancer
2004 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Ny Diagnostik och Behandling av Patienter med Binjurebarkscancer
Abstract [en]

Adrenocortical cancer (ACC) is a rare disease that is often difficult to diagnose, and therefore often presents at an advanced stage. Various cytotoxic treatments have been tried with little success. Evaluation of new diagnostic methods and improvement of medical therapies are therefore crucial.

The diagnostic potential of 11C-metomidate positron emission tomography (PET) was evaluated in eleven ACC patients. PET visualized all viable tumors with high tracer uptake, including two lesions that CT failed to detect. Necrotic or fibrotic tumors were PET negative. Medication with adrenal steroid inhibitors and chemotherapy may decrease the tracer uptake.

We performed a phase-II study with streptozocin and o,p’-DDD (SO) combination therapy in 40 ACC patients. The SO therapy was found to have impact on the disease-free interval (P = 0.02) as well as on survival (P = 0.01) in patients who received adjuvant therapy after curative resection. Complete or partial response was obtained in 36.4% of patients with measurable disease.

The efficacy and tolerability of combination therapy with vincristine, cisplatin, teniposide, and cyclophosphamide (OPEC) were evaluated in eleven patients with advanced ACC after failure of SO therapy. The median survival was 21 months from the start of treatment. A partial response was achieved in two patients. Adverse events were mainly restricted to grade 1-2 toxicities, and grade 3 toxicities were observed in only two cycles.

We tested 21 ACC tumors to analyze the expression of receptor tyrosine kinases and 15 ACC for mutation analysis of c-Kit exon 11, which can be targeted by antagonists such as imatinib. All ACCs expressed one or more kinases: c-Kit in 19 ACC and phospho-c-Kit in three while 14 ACCs expressed PDGFR-beta, suggesting the potential usefulness of tyrosine kinase inhibitors. No c-Kit mutations were detected in exon 11. Further evaluation of other mutations targeted by this drug may be needed.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2004. 74 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1346
Keyword
Medicine, Adrenocortical cancer, Positron Emission Tomography, Metomidate, Combination chemotherapy, Streptozocin, op'-DDD, OPEC, Disease-free Interval, Survival, Responses, Side effects, Receptor protein-tyrosine kinases, c-Kit, Phospho-c-Kit, PDGFRβ, Mutation, Imatinib, Medicin
National Category
Dermatology and Venereal Diseases
Identifiers
urn:nbn:se:uu:diva-4243 (URN)91-554-5954-4 (ISBN)
Public defence
2004-05-26, Enghoffsalen, Entrance 50, ground floor, University Hospital, SE-751 85, Uppsala, 13:15
Opponent
Supervisors
Available from: 2004-05-03 Created: 2004-05-03Bibliographically approved

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