Intra-pleural treatments

Intra-pleural treatments

The intracavitary administration of chemotherapy may seem logical after tumor cytoreduction surgery.

Hyperthermia potentiates cytotoxicity and tissue penetration. The studies carried out (Richards, 2006; Monneuse, 2003; Van Ruth, 2003; Yellin, 2001; Pass, 1997) focused on too few patients to be able to formally assess the potential benefit of this technique. The toxicity is not negligible.

Intrapleural ± hyperthermia chemotherapy cannot be offered outside of clinical trials.

Intrapleural photodynamic therapy is currently being evaluated in clinical trials.

In total, there is currently no place for intra-pleural treatments, outside of clinical trials.

 

Summary of systemic treatment recommendations:

Standard:

The standard chemotherapy for malignant mesothelioma is based on the combination cisplatin 75 mg / m2 - pemetrexed 500 mg / m2 administered every 3 weeks with vitamin supplementation B12 (1000 μg IM every 9 weeks) and B9 (350 to 1000 μg / day) to be started at least 7 days before the start of chemotherapy. 6 cycles maximum, without maintenance by pemetrexed.

The addition of bevacizumab to this chemotherapy at a dose of 15 mg / kg every 3 weeks, followed by maintenance with bevacizumab alone makes it possible to significantly improve survival in patients aged less than 75 years, eligible for bevacizumab, but this anti VEGF is

in this indication used outside the Marketing Authorization and non-refundable.

If cisplatin is contraindicated, it may be suggested to replace cisplatin with carboplatin (AUC 5) in combination with pemetrexed alone. In contrast, the triple carboplatin-pemetrexed-bevacizumab combination has not shown superiority compared to carboplatinpemetrexed.

The early introduction of chemotherapy in unresectable forms seems preferable to a delayed initiation of the onset of symptoms in patients who are not symptomatic at the time of diagnosis.

Options: after discussion in a multidisciplinary consultation meeting:

Monotherapy with pemetrexed 500 mg / m2 administered every 3 weeks with vitamin B9-B12 supplementation or with gemcitabine may be offered in elderly or frail patients.

Vinorelbine as a weekly monotherapy (30 mg / m2 for 12 weeks) is an alternative to multidrug therapy, especially in elderly patients, in poor general condition or in cases of renal failure contraindicating the use of pemetrexed.

In the second line, there is no validated treatment. However, resuming a pemetrexed-based regimen may be considered in the event of a prolonged free interval (expert consensus).

Chemotherapy with pemetrexed, vinorelbine gemcitabine, may be considered a second-line alternative.

No indication currently validated for immunotherapy outside of therapeutic trials.

5.6. Multimodal approach to treatment

Enlarged pleuro-pneumonectomy (EPP) can be discussed in case of:

MPM of non-predominantly sarcomatoid type

clinical and / or pathological stage I or II (± III)

patient eligible for a pneumonectomy (ventilatory reserve, absence of comorbidity (cardiovascular))

patient eligible for neo-adjuvant / adjuvant chemotherapy

patient eligible for hemithoracic radiotherapy for curative purposes.

 

EORTC and CALGB scores can be calculated in these patients but the value to define a “favorable prognosis” should be validated in a prospective trial.

5.6.1. Rationale for the multimodal approach

Surgery alone is not curative because carcinologically satisfactory resection margins are difficult to obtain. The pleura, especially at the pericardial and mediastinal level, cannot be resected with a margin of 1 to 2 cm. Consequently, any surgical resection is considered in R1 (Rusch, 2001). These observations are at the origin of multimodal treatment.

The irradiation of a hemithorax is limited by the organs at risk (contralateral lung, liver, heart in particular but also spinal cord and esophagus). Therefore, it is difficult to deliver a total dose> 54 Gy in such a volume. Sophisticated techniques guided by surgeons and pathologists are needed.

5.6.2. Patients concerned

Due to the importance of the surgical procedure and the associated treatments, the files of potential candidates must be carefully examined before undertaking a multimodal therapeutic approach:

physical examination: retraction of the hemithorax which is a sign of advanced disease, absence of intercostal or abdominal nodule

respiratory functional exploration: sufficient postoperative ventilation

satisfactory heart condition with no elevation in pulmonary artery pressure or rhythm disturbance.