Adding hyperthermia increased chemotherapy benefit in sarcoma treatment

Regional hyperthermia added to chemotherapy improved local PFS and disease-free survival in patients with soft tissue sarcoma.

Preoperative and postoperative chemotherapy plus regional hyperthermia were more clinically effective than chemotherapy alone in patients with high-risk soft tissue sarcoma, according to findings from a phase-3 study.

“This therapeutic strategy offers a new treatment option and can be integrated in the multimodal treatment approach for these patients,” researchers wrote.

Participants were recruited from six centers in Germany, one in Norway, one in Austria and one in the United States from July 1997 to November 2006. The researchers randomly assigned 341 patients neoadjuvant chemotherapy alone (etoposide, ifosfamide and doxorubicin; n=172) or chemotherapy plus regional hyperthermia (n=169).

The results were published in Lancet Oncology, and originally presented in part last year at the ECCO 15 – ESMO 34 Multidisciplinary Congress.

Survival better with hyperthermia

Fewer patients had local progression with chemotherapy plus hyperthermia (n=56) vs. with chemotherapy alone (n=76) after a median follow-up of 34 months. Patients assigned to chemotherapy alone were more likely than patients assigned combination therapy to experience local progression or death (HR=0.58; 95% CI, 0.41-0.83).

At two years, the absolute difference between local PFS was 15% (95% CI, 6-26); local PFS was 76% for combination therapy vs. 61% for chemotherapy alone. The HR for DFS was 0.70 (95% CI, 0.54-0.92) for the combination group compared with the chemotherapy alone group.

OS did not differ between groups with 74 deaths in the combination group and 79 deaths in the chemotherapy alone group (HR=0.88; 95% CI, 0.64-1.21). In per-protocol analysis, OS was better in the combination therapy group (HR=0.66; 95% CI, 0.45-0.98). Also, the response rate was higher in the combination group vs. the chemotherapy alone group (28.8% vs. 12.7%; P=.002).

Grade-3 or -4 leukopenia was more common with combination therapy vs. chemotherapy alone (77.6% vs. 63.5%; P=.005). Mild to moderate hyperthermia-related adverse events included pain (40.5%), bolus pressure (26.4%) and skin burn (17.8%); severe adverse events included pain (4.3%), bolus pressure (4.9%) and skin burn (0.6%).

There were two deaths attributable to combination treatment and one to chemotherapy alone.

“At present the benefits of this new intervention is restricted to patients with high-risk soft tissue sarcoma,” the researchers wrote. “Whether a similar benefit will be seen in lower-risk patients, and whether the safety profile will be the same, and hence the trade-off between benefit and harm worthwhile, remains to be established.”

Current routine clinical practice consists of preoperative and postoperative first-line chemotherapy, such as ifosfamide and doxorubicin with regional hyperthermia, and preoperative radiotherapy if possible, the researchers added.

Issels RD. Lancet Oncol. 2010;doi:10.1016/S1470-2045(10)70071-1.