http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15929134&query_hl=1

http://www3.interscience.wiley.com/cgi-bin/abstract/110506993/ABSTRACT

Research Article

Role of heat treatment in childhood cancers: Distinct resistance profiles of solid tumor cell lines towards combined thermochemotherapy

Anette Debes, PhD 1, Reinhart Willers, PhD 2, Ulrich Göbel, MD 1, Rüdiger Wessalowski, MD 1 *
1 Clinic of Pediatric Oncology, Hematology and Immunology, Heinrich-Heine-University, Düsseldorf, Germany
2 Computer Center, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany

email: Rüdiger Wessalowski (wessalowski@med.uni-duesseldorf.de)

*Correspondence to Rüdiger Wessalowski, Clinic of Pediatric Oncology, Hematology and Immunology, Heinrich-Heine-University, Moorenstreet 5, 40225 Düsseldorf, Germany.

Funded by:
Elterninitiative Kinderkrebsklinik e.V. Düsseldorf

Keywords
chemosensitivity • pediatric tumors • thermosensitivity • XTT-assay

Abstract

Background
Since information on the efficacy of hyperthermia in combination with chemotherapy on pediatric tumors is limited, we performed a systematic analysis on the synergistic effects of a combined application of heat and chemotherapy on 20 tumor cell lines derived from patients with neuroblastomas, Ewing tumors, germ cell tumors (GCT), and osteosarcomas.

Methods
Cisplatin (cDDP), a cross-linking agent, and etoposide (VP-16), a topoisomerase II inhibitor, were examined either alone or in combination with heat (42°C, 43°C) by using the XTT-assay [1].

Results
Our data demonstrate that heat stress at 43°C for 1 hr, but not at 42°C, leads to a notable cytotoxic effect on the different tumor cells. The comparison of mean survival fractions reveals values between 62% for neuroblastoma cells and 76% for Ewing tumor cells. Analyzing the sensitivity to chemotherapy alone, our results show that cDDP (5 g/ml) reduces cell growth to 47% in Ewing tumor cells, to 61% in neuroblastoma cells, to 75% in GCT cells, and to 76% in osteosarcoma cells. Treatment with VP-16 (10 g/ml) decreases cell survival to mean values between 58% (neuroblastomas) and 77% (osteosarcomas). Simultaneous application of heat and chemotherapy enhances synergistically cDDP cytotoxicity in all tumor types tested, whereas the efficacy of VP-16 is only slightly influenced by additional application of hyperthermia. The cytotoxicity of cDDP (5 g/ml) can be increased by a factor of between 1.5 and 2.5 at 42°C and from 2.6 to 14.0 at 43°C. Furthermore, the results show that the sensitivity to heat (43°C) as well as the sensitivity to chemotherapy and combined thermochemotherapy varies considerably between cell lines of the same tumor group.

Conclusions
Simultaneous application of hyperthermia synergistically enhances the cytotoxicity of the alkylating agent cDDP, but not of the topoisomerase II inhibitor VP-16, in a defined spectrum of cell lines from different pediatric tumor entities.

© 2005 Wiley-Liss, Inc.

1) A Children's Oncology Group Phase I Study of Bevacizumab in Refractory

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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=15923805


Am J Clin Oncol. 2005 Jun;28(3):301-9.

http://www.amjclinicaloncology.com/pt/re/ajco/abstract.00000421-200506000-00015.htm

Long-term follow up of high-dose chemotherapy with autologous stem cell
rescue in adults with Ewing tumor.

Laurence V, Pierga JY, Barthier S, Babinet A, Alapetite C, Palangie T,
de Pinieux G, Anract P, Pouillart P.

Department of Medical Oncology, Institut Curie, Paris, France.

Ewing tumors remain of poor prognosis, with 5-year overall survival of
55% to 65% in localized patients and not exceeding 25% in primarily
metastatic disease. Several reports, mainly in children, have reported
that some patients with poor-risk Ewing tumors may benefit from
high-dose chemotherapy (HDCT) with autologous stem cell rescue. This
retrospective study analyzed 46 patients treated in our institution
between 1987 and 2000 for localized or primary metastatic Ewing tumors
by HDCT followed by stem cell rescue. Median follow up was 7.1 years.
Median age was 21 years (range, 15-46 years). Twenty-two percent of
patients had metastases at diagnosis. The tumor site was axial in 56% of
patients. Median tumor size was 9.5 cm. The treatment regimen consisted
of induction chemotherapy, local treatment, maintenance chemotherapy,
and consolidation HDCT based on alkylating agents. No toxic death was
observed in the intensive therapy phase. Five-year overall survival and
progression-free survival were 63 +/- 7.7% and 47 +/- 7.6%,
respectively. Pejorative prognostic factors in this population were
metastases at diagnosis (5-year overall survival 34% vs.71%, P = 0.017)
and poor pathologic response (5-year overall survival 44% vs.77%, P =
0.03). This retrospective study shows a high long-term survival rate
with high-dose chemotherapy in adults.

PMID: 15923805 [PubMed - indexed for MEDLINE]