The timing of additional chemotherapy may influence the survival of certain patients with malignant pleural mesothelioma (MPM) who undergo radical surgery, according to a recent retrospective study published in Lung Cancer.
The study, “How does the timing of chemotherapy affect outcome following radical surgery for malignant pleural mesothelioma?“, was developed by researchers at the University Hospitals Leicester, and suggests that MPM patients with a poorer prognosis, such as those with non-epithelioid cell type and pathological lymph node disease, have a survival advantage if treated with chemotherapy immediately after surgery.
Treating MPM patients with a combination of radical surgery and chemo-radiotherapy has been linked to better survival and disease control. However, chemotherapy can be administered in a neo-adjuvant setting (prior to surgery), adjuvant setting (within three months after surgery), or delayed until signs of disease progression, and there is little evidence regarding the optimal timing of additional chemotherapy.
Annabel J. Sharkey and colleagues investigated whether the timing chosen for chemotherapy could influence the outcomes of those fit to receive it.
They examined data from 229 MPM patients undergoing surgery, either extrapleural pnemonectomy or extended pleurectomy-decortication, and compared the outcomes of four distinct groups: those who received neo-adjuvant chemotherapy, those who received true adjuvant therapy, patients who were treated upon disease progression, and those who were unfit for chemotherapy.
Consistent with previous data, the researchers showed that patients unfit for adjuvant chemotherapy had a significantly shorter overall survival (OS) than any of the other three groups. However, the timing of chemotherapy did influence the overall survival (OS) or progression-free survival (PFS) in patients able to undergo such treatment.
To exclude that the benefit was being masked, these patients were further analyzed according to their subtypes. This time, the investigators found that patients with non-epithelioid histology had significantly improved overall survival when treated with true adjuvant chemotherapy, compared to patients who received delayed chemotherapy (15.6 versus 8.2 months OS). Similarly, patients with lymph node positive tumors showed increased OS and PFS when treated with true adjuvant chemotherapy rather than with delayed chemotherapy.
But those with epithelioid tumors did not significantly benefit from chemotherapy given in the adjuvant setting. For these patients, “it may be beneficial to reserve chemotherapy until there is evidence of progression in order to avoid both chemoresitance, and the early utilisation of the only proven line of therapy available, except perhaps in the context of pathological nodal disease,” the authors wrote.
Similar analysis done on patients who had received platinum/premetrexed therapy as first line treatment also showed similar results: there was no overall effect of the timing of chemotherapy, but patients with non-epithelioid disease had improved OS, and those with lymph node metastasis had improved PFS, when immediate adjuvant chemotherapy was given.
Importantly, this effect was stronger than when all the chemotherapeutic agents were considered, suggesting that current chemotherapy protocols should be standardized to include this combination therapy.
“We have been unable to show an outstanding benefit of one strategy over the others, but the decision regarding timing of chemotherapy should be influenced by the cell type and pathological nodal stage of the tumour,” the researchers wrote. “In those with the poor prognostic factors of non-epithelioid cell type, and/or positive lymph nodes, we suggest that additional chemotherapy given in the immediate post-operative setting may be beneficial.”