Antiangiogenic metronomic chemotherapy and hyperthermia in the palliation of advanced cancer.

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Franchi F, Grassi P, Ferro D, Pigliucci G, De Chicchis M, Castigliani G, Pastore C, Seminara P.

Department of Clinical Medicine, University of Roma La Sapienza, Italy.

Among a large series of cancer patients treated with a combination of chemotherapy and sessions of hyperthermia, particular attention was given to a specific group of patients with advanced cancer who refused standard, aggressive, treatment. In these cases, hyperthermia was associated to low-dose (metronomic) chemotherapy with. No toxicity was reported in any of our patients


Material and Methods

Overall, 198 patients were treated in our department with a combination of HT and different regimens of CHT. Out of this group, 26 patients, within the age range of 63–85 years (mean age: 75 years), with various measurable tumours were treated with Mcht combined with HT (five patients with colon cancer, four patients with lung cancer, four patients with gastric cancer, three patients with gallbladder cancer, two patients with breast cancer, two patients with soft tissue sarcoma, one patient with thyroid cancer, one patient with head and neck cancer, one patient with liver cancer, one patient with pancreatic cancer, one patient with bladder cancer and one patient with renal cancer).

For ethical reasons, patients were enrolled in this study only if they refused to receive standard CHT and after informed consent was obtained. The basic treatment plan implied: administration of Mcht over a period of 2 months (Vinblastine 1.5 mg and Mitomycin C 0.5 mg twice a week), combined with twice weekly capacitive hyperthermia sessions of 45–60 min (using a Synchroterm RF 13.56 Mhz machine), for the first 5 weeks only. If rapid progression (RP) and/or toxicity did not occur over this 2-month period, the Mcht treatment was continued until a condition of slow progression (SP) was at least maintained (see below for RP and SP). In this cohort of patients, the treatment with Mcht was carried out for 2–8 months. Six patients were lost to the follow-up. Criteria for response to this study were peculiar and were as follows: response (R) was indicated as a tumour mass reduction whatsoever; stabilization of disease (S) was indicated as a lack of tumour enlargement, provided that it was not accompanied by an increase in tumour markers and lasted for at least 8 weeks; SP was indicated as a tumour increase <30% lasting at least 8 weeks in absence of life quality (LQ) deterioration, as evaluated every 2 weeks with the QLQ-30 EORTC test  RP was indicated as a tumour increase >30% or even lesser increase if it was accompanied by LQ deterioration.



Overall, 20 patients were eligible for evaluation of response and toxicity. We observed 15% of R (three patients), 35% of S (seven patients), 30% of SP (six patients) and 20% of RP (four patients) with an apparent antitumour effect in 80% of the cases (See table above).

Median time to progression (TTP) was 7 months for responders (R), while it was 3 and 3.5 months, respectively, for patients exhibiting S and SP. None of the patients presented any signs of extrahemathological toxicity and/or any undesired side effects. A very light haemathological toxicity (only grade I thrombocytopenia) was observed in two patients (10%). However, outside the cohort of patients presented in this study, of the 85 patients who received CHT combined with hyperthermia, two patients presented a myocardial infarction and two patients presented a stroke (4.7% of thromboembolic events).

During therapy, we could detect a coagulative perturbation that deserves careful discussion. In our opinion, this experience should be matter of debate to conclude if current response criteria (WHO/UICC and RECIST) in treating cancer patients are really suitable tools to evaluate new, and non-aggressive anticancer strategies.