**4. Risks and benefits of neoadjuvant chemotherapy of malignant pleural mesothelioma**

Platinum-based chemotherapy plus gemcitabine or pemetrexed for 3 to 4 cycles followed by surgery and postoperative high-dose radiotherapy showed the best results in terms of overall and progression free survival. However, patients were selected without a control group, and a randomized controlled trial to define the best treatment is still lacking.

Multimodality treatment is long. For the remarkable physical and psychological distress at the end of this invasive approach it is important to look for a strong evidence of the benefits.

The MARS trial tried to answer the question about the benefits of extrapleural pneumonectomy in the context of trimodality treatment. The results were controversial, so the debate inside the scientific community is still open.

Some thoracic surgeons and clinicians believe there is sufficient evidence to support the use of extrapleural pneumonectomy in selected patients; on the other side, the "doubters" underline the scientific bias inside the patients' selection: the improvement in overall survival with EPP might be the result of the exclusion of patients not suitable for surgery, therefore with unfavourable features.

The MARS study was the only randomized trial which compared EPP to no EPP, showing no benefit for mesothelioma patients who underwent such surgical procedure.

The optimal treatment for malignant pleural mesothelioma is still a matter of debate not only as far as the surgery is concerned.

In the context of a multimodality treatment, chemotherapy was administered as adjuvant treatment after surgery for many years, while the administration of chemotherapy in the induction phase was recently introduced in the clinical practice.

As already mentioned, the potential benefits of preoperative chemotherapy are the early eradication of the circulating metastases and the shrinkage of tumor size; the first could reduce the rate of distant recurrences and the second could make the surgery possible for inoperable tumors or easier for operable but extensive disease. Furthermore, the difficult delivery of both radiotherapy and chemotherapy after surgery was another reason to administer chemotherapy as the first step of the trimodality protocol aiming at a better tolerance of the side effects.

On the other side the delay of the surgical procedure is a disadvantage of neoadjuvant chemotherapy, especially when chemotherapy is not effective

110 Malignant Mesothelioma

**mesothelioma** 

benefits.

impacted the patients' outcome.

pleurectomy/decortication is needed.

the debate inside the scientific community is still open.

therefore with unfavourable features.

only as far as the surgery is concerned.

tolerance of the side effects.

Overall survival was longer in those patients who were treated with pleurectomy/decortication; however gender, stage, histotype were significant factors which

In the future, a randomized study to evaluate the outcome of patients treated with

**4. Risks and benefits of neoadjuvant chemotherapy of malignant pleural** 

Platinum-based chemotherapy plus gemcitabine or pemetrexed for 3 to 4 cycles followed by surgery and postoperative high-dose radiotherapy showed the best results in terms of overall and progression free survival. However, patients were selected without a control

Multimodality treatment is long. For the remarkable physical and psychological distress at the end of this invasive approach it is important to look for a strong evidence of the

The MARS trial tried to answer the question about the benefits of extrapleural pneumonectomy in the context of trimodality treatment. The results were controversial, so

Some thoracic surgeons and clinicians believe there is sufficient evidence to support the use of extrapleural pneumonectomy in selected patients; on the other side, the "doubters" underline the scientific bias inside the patients' selection: the improvement in overall survival with EPP might be the result of the exclusion of patients not suitable for surgery,

The MARS study was the only randomized trial which compared EPP to no EPP, showing

The optimal treatment for malignant pleural mesothelioma is still a matter of debate not

In the context of a multimodality treatment, chemotherapy was administered as adjuvant treatment after surgery for many years, while the administration of chemotherapy in the

As already mentioned, the potential benefits of preoperative chemotherapy are the early eradication of the circulating metastases and the shrinkage of tumor size; the first could reduce the rate of distant recurrences and the second could make the surgery possible for inoperable tumors or easier for operable but extensive disease. Furthermore, the difficult delivery of both radiotherapy and chemotherapy after surgery was another reason to administer chemotherapy as the first step of the trimodality protocol aiming at a better

no benefit for mesothelioma patients who underwent such surgical procedure.

induction phase was recently introduced in the clinical practice.

group, and a randomized controlled trial to define the best treatment is still lacking.

Some authors reported the impairment of cardiorespiratory function as another detrimental effect of induction chemotherapy and showed an increased risk of perioperative morbidity and mortality.
