Oncologists have debated for years whether standard chemotherapy delivered before or after aggressive surgery is more effective in treating patients with mesothelioma.
The debate isn’t ending anytime soon.
The first randomized phase II clinical trial examining the issue isn’t scheduled to conclude until April 2020.
Surgical patients often are faced with this dilemma when they contemplate second opinions and decide where to receive specialized treatment.
“It often comes down to an institution’s preference, or a surgeon’s preference, or the medical oncologist’s preference, but not necessarily knowing for sure which is best for the patient,” Dr. Charles Simone, University of Maryland Comprehensive Cancer Center radiation oncologist, told The Mesothelioma Center at Asbestos.com. “So we’ve tried to answer the question for the first time.”
Past Results Not Definitive
Simone is the lead author of a recent, retrospective study on the topic that analyzed almost 400 surgical patients from the National Cancer Database.
The study could be a precursor to the ongoing clinical trial in Europe.
All had the epithelioid or biphasic subtype of pleural mesothelioma.
Half completed chemotherapy before surgery. The other half did chemotherapy treatment after surgery.
Research found no definitive advantage — either way — on when best to use chemotherapy.
The Journal of Thoracic and Cardiovascular Surgery published the study, which included these findings:
Induction Chemotherapy Followed by Surgical Resection
20.9-month median overall survival
7-day postoperative hospitalization
3.3 percent 30-day mortality
Resection Followed by Postoperative Chemotherapy
21.7-month median overall survival
6-day postoperative hospitalization
0 percent 30-day mortality
“There are pros and cons on both sides,” Simone said. “In Europe, they still like to do the chemotherapy first. Here in the United States, there is more of the mentality that if you think surgery is the best way to achieve long-term survival, why delay it? Fewer centers now are doing chemotherapy first in this country.”
Advantages and Disadvantages
According to the study, the potential advantages and disadvantages of chemotherapy before surgery include:
A more optimal full-dose delivery of chemotherapy — which could lead to tumor reduction or complete response — and a better chance at total tumor debulking.
A better idea if aggressive surgery will actually help. Tumor progression during chemotherapy usually means a poor prognosis, which would allow patients to bypass a debilitating surgery that will do more harm than good.
Difficult side effects from chemotherapy could delay or preclude surgery or increase surgical complications.
Conversely, having surgery first could limit a patient’s ability to undergo full multidisciplinary treatment, potentially eliminating the chance to undergo full-dose chemotherapy.
“This study is pretty reassuring that half the patients aren’t getting a more optimal or superior approach,” Simone said. “Both are good, accepted approaches. It’s more what the institution is comfortable with, and how the doctors are trained to do it.”
European Trial May Be More Definitive
The ongoing clinical trial is being done at centers in Belgium, France and the Netherlands. The European Organization for Research and Treatment of Cancer is sponsoring the study.
The goal is 64 patients, half of whom will undergo pleurectomy and decortication surgery followed by three cycles of pemetrexed and cisplatin chemotherapy.
A second group will receive the same chemotherapy combination before the P/D procedure.
“The primary objective of the study is to investigate the feasibility of immediate P/D, followed by chemotherapy, or deferred P/D after chemotherapy in patients with early stage malignant pleural mesothelioma,” the clinical trial authors wrote.
The trial started in 2016, hoping to determine if one method is better than the other.
Researchers plan to use the more advantageous procedure in a comparative study with either the extrapleural pneumonectomy surgery or a no-surgery control arm.