Systemic melphalan has been widely used, from oral administration to high-dose chemotherapy, in a strategy of blood and marrow transplantation [5, 6
]. The intra-arterial route is not documented. From March 2002 to December 2003, four patients with histologically confirmed liver metastases and peritoneal involvement from ovarian cancer entered this study. Median liver involvement was more than 50% and ascites was observed in three patients. All patients had platinum-resistant disease and they progressed after systemic chemotherapy with taxanes, topotecan and pegylated liposomal doxorubicin. The median age was 53 years; performance status (WHO criteria) was 2 in one patient and 1 in three. Abdominal pain was present in all patients, with a median visual analogue scale (VAS) value of 5.3. In three patients, CA125 level was high (median 12.5 U/ml).
Melphalan was infused bolus by angiographic catheter introduced in the proper hepatic artery using the Seldinger technique at a dosage of 20 mg/m2 on day 1, every 4 weeks; after each administration the CA125 catheter was removed. The response was evaluated according to WHO criteria and toxicity was graded according to the National Cancer Institute Common Toxicity Criteria.
Fifteen cycles were administered; no side-effects related to the angiographic procedure were observed. Mild haematological toxicity occurred: one case of grade 3 leukopaenia and one case of grade 3 thrombocytopaenia were observed. Three patients showed a reduction of liver metastases of more than 50%, but one showed disease progression after one cycle. In two patients we observed a significant reduction of ascites and an impressive reduction in CA125 level in the other two cases. The responders showed an improvement in performance status and a marked pain reduction (median VAS of 2.3).
After a median follow-up of 15 months (range 521) three patients were dead, with a median survival of 13 months from intra-arterial chemotherapy. The time taken to respond to chemotherapy was 3 weeks and the time taken to ascertain failure of the treatment was 4.5 months. The live patient is a responder and showed a liver and pleural progression of the disease after 5 months.
This novel therapeutic approach appears very well tolerated and feasible in heavily pretreated patients with liver metastases from platinum-resistant epithelial ovarian cancer. This approach showed an interesting activity and a significantly rapid clinical improvement.
Further studies are warranted to verify these preliminary results.
Departments of 1 Oncology and 2Radiology, City Hospital, Carrara; Departments of 3 Oncology and 4 Radiology, "C. Poma" General Hospital, Mantova, Italy
* Email: mauriziocantore{at}hotmail.com
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