|
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 In an unpublished study, he reported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
|
Title
|
Patient Group
|
Results
|
Conclusions
|
Reference
|
|
Improved Survival with interferon alpha
maintenance therapy following pleurectomy/
decortication
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-2 Regimen 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
|
Mice
|
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.
|
*** POSTED ON FEBRUARY 7, 2008 ***
|