ABSTRACT
AIM: To evaluate the effect of urotropin on the tolerance of an extreme whole body hyperthermia (WBH) regime (44.5-45.0 degrees C for 60 min) in rats, and then its application to pediatric patients with advanced cancer during WBH sessions (42.5-43.0 degrees C). METHODS: In experiments nonbred rats bearing Sarcoma 45 (Sa 45) were subjected to severe WBH with and without urotropin. Tolerance of WBH as well as tumor growth and survival of animals were monitored. Extreme WBH sessions (42.5-43.0 degrees C) + urotropin were used in multimodal treatment of 13 children with advanced, refractory or recurrent malignant tumors (42 procedures in total). RESULTS: Our experiments showed 5-fold increase in rat survival during the first two days following application of extreme WBH due to the additional administration of urotropin. This regime demonstrated a significant inhibitory effect upon the growth of Sa 45. In children with progressive malignant tumors we achieved extreme WBH regimes (up to 43.2 degrees C) using urotropin without additional toxicity and with 69% overall response rate. CONCLUSION: Extreme WBH (42.5-43.0 degrees C) could be used in the management of advanced and refractory cancer. Urotropin may play a favorable role during the procedures of extreme WBH, decreasing thermal damage to the body. Lymphocyte collection by lymphopheresis before WBH session and its reinfusion may be one of the progressive approaches for minimizing lymphocyte apoptosis.
Subject(s)
Antineoplastic Agents/adverse effects , Hyperthermia, Induced/adverse effects , Methenamine/adverse effects , Neoplasms/therapy , Adolescent , Animals , Apoptosis/drug effects , Child , Combined Modality Therapy/methods , Female , Humans , Lymphocytes/drug effects , Lymphocytes/pathology , Male , Rats , Salvage TherapyABSTRACT
Whole body hyperthermia (WBH) in combination with chemotherapy has been proven to be effective in some patients with advanced malignancies. However, only limited experience exists regarding the application of WBH with chemotherapy in children. We present the results of applying WBH and chemotherapy in five children with advanced renal cell carcinoma (RCC). WBH (3 hr, 41.8-42.5 degrees C) combined with doxorubicin (50 mg/m2) and interferon-alpha (3 MU/m2) were applied to patients after nephrectomy and lymph node dissection. Each patient received three to eight courses of treatment three times weekly. All children tolerated the combined therapy well without complications. Follow-up of 7-68 months (median: 22 months) showed no tumor progression in patients with locoregional (n = 3) and metastatic (n = 2) disease. WBH with moderate dose doxorubicin and INF-alpha might be a feasible treatment option in childhood RCC.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Renal Cell/therapy , Hyperthermia, Induced , Kidney Neoplasms/therapy , Adenocarcinoma/therapy , Adenocarcinoma, Clear Cell/therapy , Adolescent , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Carcinoma, Papillary/therapy , Chemotherapy, Adjuvant , Child , Doxorubicin/administration & dosage , Female , Humans , Interferon-alpha/administration & dosage , Lymph Nodes/pathology , MaleABSTRACT
AIM: To evaluate the summarized effect of hyperthermia and interleukin-2 (IL-2) administration on antitumor defense in tumor-bearing rats. METHODS: Nonbred rats after subcutaneous inoculation of sarcoma 45 cells were treated with whole-body hyperthermia (WBH, +42.5 degrees C, 60 min) and interleukin-2 (IL-2, 10,000 U/kg of body weight). Parameters of tumor growth and survival of animals were monitored till day 33 after tumor cell inoculation. RESULTS: Combined application of WBH and IL-2 at 5th day after tumor cell transplantation resulted in a delay of tumor growth and improvement of survival parameters in comparison with control group or animals that received separate treatment. Therapeutic efficacy of WBH combined with IL-2 was analogous to a single-dose chemotherapy with cyclophosphamide. CONCLUSION: Combined application of WBH and IL-2 is the useful approach for cancer immunotherapy.