Mesothelioma science news update

October 19, 2007

San Pedro, CA, October 18, 2007
The Law Office of Roger G. Worthington, P.C.

1. Intensity-modulated radiation therapy and 3D-conformal radiation therapy are both suitable for mesothelioma. Link here.

2. Alpha-TOS ineffective at inhibiting tumor development mice with peritoneal mesothelioma, and results in severe side effects. Link here.

3. Patient with rare pericardial mesothelioma extends average 6-month survival to 16 months with carboplatin + pemetrexed regimen. Link here.

4. Tumor serum markers CEA and SMRP were able to discriminate with high sensitivity between mesothelioma and non-small cell lung cancer; Cyfra 21.1 proved useful discriminating between normal versus malignancy. Link here.

5. Risk of mesothelioma increases from second-hand asbestos exposure, but mortality from lung cancer does not increase. Link here.


Pemextrexed shows promise in peritoneal mesothelioma

September 25, 2007

By Jill Stein

BARCELONA, SPAIN — September 24, 2007 — Pemetrexed alone or in tandem with a platinum agent shows good overall response and disease control rates in patients with peritoneal mesothelioma (PM), according to data presented here at the 14th European Cancer Conference (ECCO).

The study enrolled 109 patients with a histologic or cytologic diagnosis of peritoneal mesothelioma that was not amenable to curative surgery and was treated with pemextrexed alone or in combination with a platinum agent.

“Malignant peritoneal mesothelioma is a rare cancer, with a yearly incidence of about one or two cases per million in the U.S. and Europe, while the incidence of pleural mesothelioma is 3- to 30-fold higher in different countries, said study presenter Giacomo Carteni, MD, Director, Oncology Division, Cardarelli Hospital, Naples, Italy.

Few large studies have examined peritoneal mesothelioma, so treatment has largely been based on protocols used in patients with pleural mesothelioma, Dr. Carteni said in his poster presentation on September 24th.

The international Expanded Access Program (EAP) for pemetrexed in mesothelioma provided access to the drug before and during review by regulatory agencies.

In the trial, pemetrexed 500 mg/m2 alone or in combination with cisplatin 75 mg/m2 or carboplatin AUC 5 was given on day 1 of each 21-day treatment cycle as part of the EAP. All patients received standard supplementation with vitamin B12 and folic acid, and dexamethasone for prophylaxis.

Patients were treated until they developed progressive disease or unacceptable toxicity, or until the investigator or patient decided to halt treatment.

Pemetrexed and platinum combination was associated with a 20% or greater response rate and a 76% or greater disease control rate.

Patients in the single-agent platinum group had a 12.5% overall response rate, a 50% disease control rate, and a 41.5% survival rate at 1 year. “This is in line with their worse prognostic factors like higher median age, higher percent of patients who had undergone prior chemotherapy, and lower performance status at baseline,” Dr. Carteni said.

Hematologic toxicity was manageable in all groups and in agreement with earlier phase 3 findings, he said.

These results reported for peritoneal mesothelioma are comparable to the pemetrexed EAP in the U.S., which involved 98 patients with peritoneal mesothelioma. In that report, the overall response rate was 26% and median survival exceeded 13 months.

The study was sponsored by Eli Lilly and Company.

[Presentation title: Open-Label Study of Pemetrexed (P) Alone or in Combination With a Platinum in Patients With Peritoneal Mesothelioma (PM): Results From the International Expanded Access Program. Abstract P-6571]

Efficacy of surgery combined with perioperative intraperitoneal chemotherapy for peritoneal mesothelioma

August 6, 2007

Ann Oncol. 2007 May;18(5):827-34, Yan TD, Welch L, Black D, Sugarbaker PH.

From PubMed

In the past, peritoneal mesothelioma was regarded as a preterminal condition. The length of survival was dependent upon whether the cancer itself was aggressive or slow. The median survival was approximately 1 year after chemotherapy.

Surgery combined with intraperitoneal chemotherapy has been used as a treatment alternative, but the efficacy of this combined treatment remains to be established.

Seven prospective observational studies from six tertiary institutions were available, allowing 240 peritoneal mesothelioma patients for assessment. The median survival ranged from 34-92 months. The 1-, 3- and 5-year survival varied from 60% to 88%, 43% to 65% and 29% to 59%, respectively. This systematic review demonstrated an improved overall survival, as compared to historical controls, using systemic chemotherapy and palliative surgery.

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A useful combination of markers for differentiating epithelioid peritoneal mesothelioma from serous papillary carcinoma of the ovary

August 3, 2007

Am J Surg Pathol. 2007 Aug;31(8):1139-1148, Comin CE, Saieva C, Messerini L., Department of Human Pathology and Oncology, University of Florence, Florence †Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Center, (CSPO), Scientific Institute of Tuscany, Florence, Italy

From PubMed

Distinguishing between epithelioid peritoneal mesothelioma and papillary serous carcinomas involving the peritoneum can be difficult because of overlapping morphologic features. Immunohistochemistry may facilitate a correct diagnosis. However, since no single antibody has demonstrated absolute sensitivity and specificity for either mesothelioma or serous carcinoma, the diagnosis is based mainly on the combined use of several markers.

The purpose of this study was to ascertain how well a series of mesothelial markers work, including more recently investigated antigens such as h-caldesmon (h-CD) and D2-40, using receiver operating characteristic curve analysis, to identify an appropriate selection of antibodies for differentiating between epithelioid peritoneal mesothelioma and serous papillary carcinoma of the ovary.

Fifteen cases of epithelioid peritoneal mesothelioma and 40 cases of papillary serous carcinoma of the ovary (25 primary and 15 metastatic to the peritoneum) were immunostained for h-CD, D2-40, calretinin, cytokeratin 5/6, thrombomodulin, estrogen and progesterone receptors (ER and PR), Ber-EP4, B72.3, CA19-9, and CD15. h-CD and calretinin showed the highest sensitivity (100%), followed by D2-40 (93.3%) and cytokeratin 5/6 (93.3%); thrombomodulin had the lowest sensitivity (60%). h-CD and thrombomodulin had the best specificity (95%) for mesothelioma, followed by calretinin (87.5%), D2-40 (80%), and cytokeratin 5/6 (72.5%). Among carcinoma markers, ER and Ber-EP4 demonstrated the highest sensitivity (95%) followed by B72.3 (72.5%), PR (65%), CA19.9 (60%), and CD15 (45%).

The specificity of the nonmesothelial markers was 100%, except for Ber-EP4 (93.3%). The relationship between the values of sensitivity and specificity of each marker using receiver operating characteristic analysis permitted the identification of h-CD, calretinin, ER, and Ber-EP4 as the markers with the best performance in differentiating epithelioid peritoneal mesothelioma from serous papillary carcinoma of the ovary.

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Multimodal treatment for multicystic and well-differentiated papillary peritoneal mesothelioma

August 1, 2007

Ann Surg Oncol. 2007 Jul 28,     Baratti D, Kusamura S, Nonaka D, Oliva GD, Laterza B, Deraco M., Department of Surgery, National Cancer Institute, Milan, Italy,

Abstract from PubMed

Multicystic peritoneal mesothelioma (MPM) and well-differentiated papillary peritoneal mesothelioma (WDPPM) are exceedingly uncommon lesions with uncertain malignant potential and no uniform treatment strategy. The aim of the current study was to review our experience with cytoreduction and hyperthermic intraperitoneal chemotherapy (HIPEC) in these clinical settings.

Four women with MPM and eight with WDPPM underwent 13 procedures of cytoreduction and close-abdomen HIPEC with cisplatin and doxorubicin. Seven patients had recurrent disease after previous debulking (one operation in five patients, two in one, four in one). Potential clinicopathological prognostic factors were assessed.

Optimal cytoreduction was performed in 12 of 13 procedures. Median follow-up was 27 months (range 6-94). One grade 4 postoperative complication and no operative mortalities occurred. One patient underwent the procedure twice due to locoregional MPM recurrence. Transition of typical WDPPM to malignant biphasic mesothelioma was documented in one patient who died of disease progression following incomplete cytoreduction and HIPEC.

Following multimodality treatment, 5-year overall and progression-free survival were 90.0% and 79.7%, respectively. Progression-free survival following previous debulking surgery was statistically worse. Incomplete cytoreduction and poor performance status correlated to both reduced overall and progression-free survival after cytoreduction and HIPEC.

MPM and WDPPM are borderline tumors capable of transformation into potentially lethal processes. Definitive tumor eradication by means of cytoreduction and HIPEC seems more effective than debulking surgery in preventing disease recurrence or transition to aggressive malignancies.

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