| Abstract | Many women diagnosed with invasive breast cancer have undetected occult metastases at the time of their primary tumour diagnosis. The development and growth of these micro-metastases relies heavily on angiogenesis. Therefore, administering an angiogenesis-blocking treatment from the time of diagnosis could reduce the incidence of metastasis and, ultimately, increase patient survival. It is hypothesized that an antiangiogenesis strategy combining fever-range whole-body hyperthermia (FR-WBH) and metronomic chemotherapy could inhibit the development of metastatic disease with minimal toxicity. To test this theory, a low, daily dose of the topoisomerase-I inhibitor irinotecan hydrochloride (CPT-11) was administered over a prolonged period of time to rats bearing the highly metastatic MTLn3 mammary adenocarcinoma primary tumour surgically excised on day 12 after implantation. The metronomic CPT-11 was combined with long-duration, low-temperature, fever-range whole body hyperthermia (FR-WBH). This systemic hyperthermia enhances chemotherapy-induced cytotoxicity as well as immunological activity. Both the group treated with FR-WBH alone and the combined FR-WBH + CPT-11 group had delayed onset and reduced incidence of axillary lymph node metastases compared to control (p < 0.05). Combination therapy of FR-WBH + CPT-11 resulted in a significantly greater inhibition of axillary lymph node metastasis volume compared to both control and CPT-11 alone (p < 0.02) at day 16. Interestingly, none of the therapies significantly affected inguinal lymph node metastases. Lung metastases were decreased by 36% at the time of death in rats treated with FR-WBH + CPT-11, by 25% in the CPT-11 alone group and by 14% in the FR-WBH alone group. Rats treated with FR-WBH, + CPT-11 survived significantly longer (35%) than control animals (p < 0.04). Neither significant body weight loss nor gastrointestinal toxicity was observed in any group. These data suggest that, after excision of the primary tumour, FR-WBH and metronomic CPT-11 can be safely combined to reduce distant lymph node and lung metastases and, thus, to increase survival. |
| Authors | K Sumiyoshi, F R Strebel, R W Rowe, J M C Bull
(Affiliation: The Division of Oncology, The Department of Internal Medicine, The University of Texas-Houston Medical School, 6431 Fannin Street, Houston, TX 77030, USA.)
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| Journal | International journal of hyperthermia : the official journal of European Society for Hyperthermic Oncology, North American Hyperthermia Group
(Int J Hyperthermia)
2003 Mar-Apr
Vol. 19
Issue 2
Pg. 103-18
ISSN: 0265-6736 England |
| PMID | 12623634
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
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| Chemical References |
- Antineoplastic Agents
- irinotecan
- Camptothecin
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| Topics |
- Adenocarcinoma
(drug therapy, pathology, therapy)
- Animals
- Antineoplastic Agents
(administration & dosage, adverse effects)
- Camptothecin
(administration & dosage, adverse effects, analogs & derivatives)
- Combined Modality Therapy
- Female
- Hyperthermia, Induced
(adverse effects)
- Mammary Neoplasms, Experimental
(drug therapy, pathology, therapy)
- Neoplasm Metastasis
(drug therapy, therapy)
- Rats
- Rats, Inbred F344
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