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Alternative Therapies: Keeping The Beast At Bay


A few leading surgeons have taken steps to experiment with new compounds designed to delay tumor recurrence and manage it at tolerable levels. These doctors recognize that eradication may be the ideal, but until then it's best to try to tame the beast. Dr. Robert Cameron at UCLA has achieved promising results by having his patients take a daily injection of low dose interferon-alpha after surgery and radiation. In an unpublished study, he reported median survival of greater than 36 months for this particular multi-modal therapy.

Dr. Harvey Pass is another surgeon at the forefront of finding new and better compounds to delay tumor recurrence. As an example, Dr. Pass performed a clinical trial in which he had his post-surgery patients, either PD or EPP, take tetrathiomolybdate in pill form, an anti-angiogenic copper chelate compound that he describes as "maintenance" therapy. For stage 1 or 2 patients he has reported a time to progression of 18.5 months, which is encouraging but requires validation in a larger trial.

Although promising, neither study has been tested in a randomized clinical trial due to lack of funding. For more information on novel treatments, see Chart - "Alternative therapies: Interleukin, interferon, and gene therapy."

Chart : Alternative therapies: Interleukin, interferon, and gene therapy


Patient Group




Improved Survival with interferon alpha maintenance therapy following pleurectomy/

and radiation for malignant pleural mesothelioma

139 patients with malignant pleural mesothelioma were evaluated. 65 patients were eligible and underwent surgery.

The median overall survival from the time of the operation was 13.2 months (entire group), 17.7 mo (group completing surgery and radiation), and a remarkable and highly statistically significant >>37months for the group receiving interferon maintenance therapy

Complete pleurectomy/
decortication and postoperative radiation therapy may provide similar survival to the more radical procedure of extrapleural pneumonectomy particularly in advanced stage disease. In addition,

interferon alpha maintenance therapy may provide substantial improvement in survival over existing therapies. Further studies are warranted, and mechanisms of this effect are being investigated.

PD + IMRT + Interferon = >37 months median survival

Cameron et al, presentation to the Society of Thoracic Surgeons. Jan 2006.

A phase II trial of Tetrathio-
molybdate [TM] after cytoreductive surgery for malignant pleural mesothelioma (MPM)

34 cytoreduced malignant mesothelioma patients

24 month overall survival, 24 month progression free survival
Stage I/II (n=13) 60% 69%
Stage III (n=17) 23% 0%

TM has antiangiogenic effects in postoperative MPM patients and the VEGF serum level is a robust biomarker in this therapy. TM has minimal toxicity and is at least comparable in efficacy to previous multimodality trials of cytotoxic agents for MPM. TM should be evaluated for use with standard MPM regimens, as well as for post surgical maintenance monotherapy.

Pass et al, American Society of Clinical Oncologists' annual meeting. 2004.

Interleukin-4 Receptor Cytotoxin as Therapy for Human Malignant Mesothelioma Xenografts

13 mesothelioma patients

PE38KDEL mediated a dose-dependent decrease in tumor volume and a dose-dependent increase in survival.

The chimeric protein, IL-4(38-37)-PE38KDEL, has potent anti-tumor effects against MPM both in vitro and in vivo.

Cameron et al, Ann Thorac Surg. 2004 Aug; 78(2):436-43.

Combined Epirubicin and Interleukin-2Regimen in the Treatment of MM: A Multicenter Phase II Study of the Italian Group on Rare Tumors

21 chemotherapy naïve malignant mesothelioma patients

Only one patient achieved a partial response, resulting in an overall response rate of 5% (1/21) with a median progression-free and overall survival of 5 and 10 months.

These results do not support the use of such a combination in the management of malignant mesothelioma.

Bretti et al, Tumori. 1998 Sep-Oct;84 (5):558-61.

Interleukin-2 in combination with tamoxifen in malignant pleural mesothelioma

25 mesothelioma patients

Of 25 patients treated in this investigation, a promising median survival of 15.1 months was observed for the whole group.

The overall toxicity of the combination of IL-2 and tamoxifen was found to be acceptable, consisting predominantly of skin rashes and mild flu-like symptoms.

Ulsperger et al, Eur J Cancer. 2001; 37(suppl 6):45. Abstract 154.

Cytokine gene therapy of mesothelioma. Immune and anti-tumor effects of transfected interleukin-12


AB1-IL-12 induced systemic immunity that was effective at reducing the incidence of parental AB1 tumor at a distal site, but its effects were dose-dependent.

Paracrine secretion of IL-12, generated by gene transfer, can induce immunity against MM that can act locally and also at a distant site. In addition, there was no evidence of toxicity, which has been associated with the systemic administration of IL-12.

Caminschi et al, American Journal of Respiratory Cell and Molecular Biology. 1999 Sep; 21:347-356.