Longer Survival with Pleurectomy / Decortication and Interleukin 2

“The Italians all talk funny, I don’t know what they say, I can’t find a chili pizza, for any price I pay…” Freddy King, Living in the Palace of the King

Discussion of “A phase II study of intrapleural immune-chemotherapy, pleurectomy/decortication, radiotherapy, systemic chemotherapy and long-term sub-cutaneous IL-2 in stage II-III malignant pleural mesothelioma” by Marco Lucchi et al., European Journal of Cardio-thoracic Surgery, 2007

Patients considering surgical treatment for their malignant pleural mesothelioma have a difficult time choosing between the extrapleural pneumonectomy (EPP) and the pleurectomy/decortication (P/D). The difficulty arises because there has never been a randomized clinical trial testing which type of surgery is superior. As a result, surgical data comparing the two procedures typically consists of looking back on a series of previous surgeries and trying to compare the data in a “retrospective study.”

The problem with retrospective studies for pleural mesothelioma is that patients were not randomly assigned into the EPP or the PD group, meaning that in many cases patients received the treatment because the surgeon thought that either EPP or PD was better in that particular case. For a surgical procedure to be scientifically tested, it must be randomly assigned. The second problem with retrospective series is that patients are not selected in a uniform way, so there is no true baseline of factors and characteristics against which the final results of the study can be compared.

Dr. Marco Lucchi and his team of Italian researchers recently published a study which, although it did not compare EPP with PD, did select surgical candidates according to uniform criteria and followed their progress for almost six years after surgery. The results were very promising for patients considering pleurectomy/decortication combined with immunotherapy.

26-month survival with Interleukin-2

On the West Coast, Dr. Robert Cameron at UCLA’s David Geffen School of Medicine has utilized interleukin-2 as a therapeutic agent in his multimodal treatment of mesothelioma for the last several years. Immunotherapy such as interleukin-2 has been shown to have an effect on humans and animals, and the Lucchi study decided to use it in addition to pleurectomy/decortication, chemotherapy, and radiation for a four-part multimodal therapy.

Interleukin-2 is typically depleted by cancer tumors, and pleural mesothelioma drastically reduces the level of IL-2, which is an entity that greatly boosts the body’s immune response to help fight off cancer cells. By adding IL-2 to the treatment mix, some doctors believe that the body’s own cancer fighting abilities can be boosted.

After following up patients on average for 59 months, with the longest follow up 81 months, median survival was 26 months, which is significantly better than the survival time that most patients with pleural mesothelioma can expect. Of the 49 patients in the study, 60% lived for two years after diagnosis and 23% lived for five years. No patients died during or immediately after surgery. The less radical PD results in less stress on the body and anecdotally in higher quality of life since the surgery spares the lung, which is amputated in the EPP.

Implications for patients considering surgery

Dr. Lucchi’s study has several important implications for patients considering surgical treatment for pleural mesothelioma. First, the most important factor predicting survival in the study was not cellular subtype (epithelial, biphasic, or sarcomatoid), lymph node status, or stage of cancer. The most important factor was the patient’s performance status at the time of diagnosis.

Second, Dr. Lucchi’s study did not include any stage I patients. All patients who were stage I received the EPP. Thus, as we discussed above, the surgeons may have eliminated many patients from PD surgery who could have received even greater benefit from PD with IL-2 due to their earlier stage cancer. Wrongly assuming that EPP was the preferable treatment would have impacted the study’s results, especially since the study showed that the most important factor for survival was not tumor stage but performance status. The need for a randomized clinical trial that compares these two surgical techniques cannot be over emphasized.

Third, this study confirms the idea that the best treatment for mesothelioma may likely depend on avoiding overly aggressive treatment with each of the modalities. This regimen with four different treatment modalities differs from the mainstream because rather than hitting the cancer with “everything in the arsenal at maximum force,” it accepts mesothelioma as an already advanced disease at the time of diagnosis that is better handled with an eye towards management and quality of life than with an eye towards a knock-out, out of the ballpark cure, given the state of current treatments.

*** POSTED OCTOBER 20, 2008 ***