Intraperitoneal hyperthermic perfusion chemotherapy of patients with chemotherapy-resistant peritoneal disseminated ovarian cancer.

The purpose of this article is to evaluate in a prospective, open-label clinical trial the feasibility and efficacy of intraperitoneal hyperthermic perfusion chemotherapy (IPHC) on the survival and quality of life of patients with advanced, peritoneal disseminated ovarian cancer. Thirty-six patients with ovarian cancer were accrued for the study, their selection being based on their progression following different systemic therapies with anti-neoplastic (multiple chemotherapy-resistant or -refractory) agents. The average number of chemotherapy cycles given before the first IPHC was 12.5. The patients' average Karnofsky-performance status was 60% and 17 out of 36 patients had ascites before IPHC. The input temperature of the solution for abdominal lavage was 48-49 degrees C: the intraperitoneal temperature was 42-43 degrees C. The flow-rate of the solution for heat exchange was 190-220 ml/min with treatment lasting 1 h at temperatures greater than or equal to 42 degrees C. Median overall survival time (MOS) from first diagnosis of disease (1stDx) was 49 +/- 8 months and from the first IPHC-treatment 19 +/- 4 months. The observed 1-year overall survival rate (OSR) of all patients from the start of the first IPHC was 65 +/- 8% and the 5-year OSR was 16 +/- 7%. Malignant ascites vanished within less than 3-5 IPHCs. Quality of life could be improved. The adverse effects were mild especially compared to systemic chemotherapy. In 3 out of 162 treatments, peritoneal disturbances with symptoms of subileus were observed. We conclude that IPHC is technically feasible, safe, and associated with a marked prolongation of survival and improvement in quality of life. Even heavily pretreated patients could be treated safely. Some patients did respond to IPHC even after 25 IPHC treatments. From these results, it can be concluded that IPHC may also improve the treatment outcome of patients with ovarian cancer as salvage therapy, in second-line treatment or even as consolidation or maintenance therapy following induction chemotherapy to patients with suboptimal stage III and IV disease. This should be demonstrated in randomized controlled studies.

Effects of lithium on thrombopoiesis in patients with low platelet cell counts following chemotherapy or radiotherapy.

Therapy for neoplasma is limited by hematological side effects of tumor-destructive therapy and, in part, makes expensive supportive care necessary to overcome and treat leukopenia and thrombocytopenia and their consequences. Thrombocytopenia is a major clinical problem caused by chemotherapy and radiotherapy. An effective and very cost-effective option for treating moderate neutropenia is the administration of lithium carbonate. Lithium induces the release of colony-stimulating factors (CSF) and therefore stimulates proliferation of neutrophil granulocytes. Other cytokines, such as interleukin-1 (IL-1), IL-6, and tumor-necrosis factor-alpha (TNF-alpha), are also stimulated. Apart from granulocyte-macrophage-CSF (GM-CSF), there have as yet been no reports of lithium salts inducing early activating factors for the megakaryocytic lineage, such as IL-3, IL-11, stem cell factor and flt-3 ligand, or maturation factors, such as thrombopoietin (TPO). A statistically significant increase in the mean number of platelets for patients with cell counts below 150,000/microL on the commencement of treatment with lithium carbonate could be observed. Patient tolerability of lithium carbonate therapy is very good. Patients with persistent leukopenia and thrombocytopenia following chemotherapy or radiotherapy can be treated with this trace element very cost-effectively. Unfortunately this treatment has not gained acceptance in clinical oncology in the face of extremely cost-intensive treatment with recombinant GM-CSF, IL-11 or, potentially, thrombopoietin.