Heated Intrathoracic Chemotherapy Could Extend Mesothelioma Survival

Research & Clinical Trials

Patients with pleural mesothelioma undergoing aggressive surgery should consider combining it with controversial hyperthermic intrathoracic chemotherapy to extend survival, according to a recent study.

Although the procedure, also known as HITHOC, has yet to be proven effective in a randomized clinical trial – and still is being debated by mesothelioma specialists – the report has elevated its status as a potentially useful adjuvant.

“We concluded that the heated chemotherapy, delivered in a specialty center, has shown benefit,” researcher Alan G. Dawson told The Mesothelioma Center at Asbestos.com. “It should have a place in the multimodality approach to treatment.”

Dawson studies malignant pleural mesothelioma with the Thoracic Oncology Research Group at the University of Leicester, United Kingdom.

Annals of Surgical Oncology published this latest retrospective review in April, drawing from 598 patients in 15 different studies covering eight countries.

Pleural Mesothelioma Survival Times Rise Significantly

The results showed significant improvement for those undergoing the combination treatment as compared to those receiving the surgery and traditional systemic chemotherapy.

“I was actually quite surprised at the findings,” Dawson said. “Going in, there was a lot of skepticism. Most thought there would be no difference in survival, or not much in the way of difference. The numbers, though, show that there is.”

Overall survival of those receiving the novel combination ranged from 11 to 75 months, compared with a 5- to 36-month range for those having surgery without HITHOC. The disease-free interval ranged from 7.2 to 57 months for the combination group, compared with 12.1 to 21 months for those bypassing HITHOC.

HITHOC involves circulating a heated, high-concentration chemotherapy solution throughout the chest cavity for 60-90 minutes immediately following aggressive surgery.

The belief is that the heated chemotherapy will kill any tumor cells that evaded the surgeon, which will slow the potential cancer recurrence.

Therapy Proven with Peritoneal Mesothelioma

While HIPEC, a similar procedure used effectively for peritoneal mesothelioma in the abdominal cavity, has proven to be a huge treatment benefit, HITHOC is used in a much smaller percentage of patients alongside surgery.

Specialty centers throughout the United Kingdom all have opted against using it, although this latest report could change things. Some thoracic surgeons in the U.S. have been using it, but others have opted against it.

Very few published guidelines for treatment of pleural mesothelioma include HITHOC. The National Comprehensive Cancer Network guideline does not. The latest American Society of Clinical Oncology guideline recently addressed it, but with considerable caution.

The recommendation is that “intracavity therapies may be delivered safely in experienced centers of excellence, but that their role in improving outcome is indeterminate.”

HITHOC Comes with Risks

Dosage levels made a considerable difference in the effectiveness of the HITHOC, according to the report. The higher dosage levels led to almost double the median overall survival times. Direct application in the thoracic cavity allows for a much higher local concentration, in contrast to typical systemic therapy.

As the report illustrates, though, the HITHOC procedure is not without risks. Morbidity rates can rise with the combination treatment.

According to the report, 12 of the 15 studies included data on morbidity. Atrial fibrillation was the most common morbidity at 20.4%. Renal complications were reported in 16.8% of the patients.

Selection of Mesothelioma Patients Is Key

The report also emphasizes the importance of proper selection of patients in receiving the aggressive surgery and HITHOC combination.

The heated chemotherapy regimen adds another 90 minutes to an aggressive surgery that already can take anywhere from four to 8 hours, a reason some surgeons opt against using it.

Traditionally, multimodal therapy consisting of surgery, radiation and systemic chemotherapy has been used to obtain extended survival, but recent years have included these smaller studies with HITHOC.

Two-year survival rates in this report ranged from 25% to 67%, while three-year survival rates ranged from 17% to 42%.

“It’s never been proven in a randomized trial, but evidence suggests there are benefits,” Dawson said. “If you are well enough to be considered for aggressive surgery, I would say you should consider the heated chemotherapy that can kill the tumor cells left behind.”

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