Hyperthermia combined with chemotherapy - Biological rationale, clinical application, and treatment results

There is substantial evidence from preclinical data that the antitumor cytotoxicity of selected chemotherapeutic agents either alone or combined with radiation can be enhanced by appropriate heat exposure (40-44 degrees C) of cells or tumor tissues. Based upon these results the integration of hyperthermia as an additional treatment modality, given simultaneously with systemic chemotherapy or in combination with radiochemotherapy, is currently tested at the clinic. Regional hyperthermia combined with chemotherapy or radiochemotherapy showed impressive results (phase II studies) at clinical relevant temperatures in locally advanced tumors of different entities in terms of objective response rate, local tumor control and relapse-free survival. Clinical protocols of well-designed phase III trials on combined treatment modalities integrating hyperthermia are rather limited but for some tumors confirm its clinical benefit. In general, the clinical approach to use hyperthermia has gained much more interest within in the field of medical oncology. One of the major reason is the substantial technical improvements made with the available commercial equipment for local or regional heating, especially in case of deep-seated lesions or systemic heating. Further testing of the potential of hyperthermia combined with chemotherapy or radiochemotherapy in prospective randomized trials are warranted. At this time, hyperthermia as an adjunct to conventional treatment strategies is recommended in the setting of clinical protocols. The results of prospective trials should answer the question for which types of local advanced or metastatic tumors hyperthermia becomes standard as part of a multi-modal treatment strategy

Ifosfamide with regional hyperthermia in soft-tissue sarcomas

For high-risk soft tissue sarcomas (HR-STS) of adults, new treatment strategies are needed to improve outcome with regard to local control and overall survival. Therefore, systemic chemotherapy has been integrated either after (adjuvant) or before (neoadjuvant) optimal local treatment by surgery and radiotherapy in HR-STS. The combination with regional hyperthermia as a new treatment strategy seems to open a new therapeutic window. Copyright (C) 2003 S. Karger AG, Basel

Feasibility and morbidity of combined hyperthermia and radiochemotherapy in recurrent rectal cancer - Preliminary results

Background: The local recurrence rate of colorectal cancer has been significantly reduced due to the use of combined radiochemotherapy. Despite this improvement regarding locally advanced tumour recurrences, the treatment strategy for pre-treated patients remains difficult and unresolved. Patients and Methods: We analysed treatment and follow-up data of 14 patients with local recurrence of rectal cancer who were treated with radiation therapy (RT), chemotherapy (CT) and regional hyperthermia (RHT) from November 1997 to December 2001. Nine of these patients had received irradiation and CT (=pre-treated patients) in the past. For this group, 30.6-39.6 Gy RT, 5-fluorouracil (5-FU) as a continuous infusion over 5 days per week (350 mg/m(2)/24 h) combined with RHT twice a week was given. The 5 remaining patients (=not pre-treated) received conformal irradiation of 45 Gy with a boost between 9 and 14.4 Gy, combined with continuous infusion of 5-FU on days 1-4, and 29-33 (500 mg/m(2)/24 h), and RHT twice a week. Response to therapy was evaluated by means of computed tomography (CT) or magnetic resonance imaging (MRI) and by clinical follow-up. Results: Among 13 evaluated cases, the overall objective response rate was 54% (5 complete responses, 2 partial responses). At mean follow-up of 13.9 months (range 5-32 months) 7 patients were alive. Conclusion: The therapeutic regimen appears to be active in the treatment of local recurrences of rectal cancer. Larger-scaled studies are needed to evaluate the potency of hyperthermia in this therapeutic strategy

Oral capecitabine in gemcitabine-pretreated patients with advanced pancreatic cancer

Objective: To date, no standard regimen for salvage chemotherapy after gemcitabine (Gem) failure has been defined for patients with advanced pancreatic cancer (PC). Oral capecitabine (Cap) has shown promising activity in first-line chemotherapy trials in PC patients. Methods: Within a prospective single-center study, Cap was offered to patients who had already received at least 1 previous treatment regimen containing full-dose Gem (as a single agent, as part of a combination chemotherapy regimen or sequentially within a chemoradiotherapy protocol). Cap was administered orally at a dose of 1,250 mg/m(2) twice daily for 14 days followed by 7 days of rest. Study endpoints were objective tumor response rate by imaging criteria (according to RECIST), carbohydrate antigen 19-9 (CA19-9) tumor marker response, time to progression, overall survival and toxicity. Results: A median of 3 treatment cycles (range 1-36) was given to 39 patients. After a median follow-up of 6.6 months, 27 patients were evaluable for response: no complete or partial responses were observed, but 15 patients (39%) had stable disease. A CA19-9 reduction of >20% after 2 cycles of Cap was documented in 6 patients (15%). Median time to progression was 2.3 months (range 0.5-45.1) and median overall survival (since start of Cap treatment) was 7.6 months (range 0.7-45.1). Predominant grade 2 and 3 toxicities (per patient analysis) were hand-foot syndrome 28% (13% grade 3); anemia 23%; leg edema 15%; diarrhea 13%; nausea/vomiting 10%, and leukocytopenia 10%. Conclusion: Single-agent Cap is a safe treatment option for Gem-pretreated patients with advanced PC. Further evaluation of Cap in controlled clinical trials of Gem-pretreated patients with advanced PC is recommended. Copyright (C) 2008 S. Karger AG, Basel