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Mesothelioma Treatment Therapy Studies

Başlatan Fussilet, Nisan 26, 2009, 05:37:05 ÖS

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Circulating CA125 in Patients with Peritoneal Mesothelioma Treated with Cytoreductive Surgery and Intraperitoneal Hyperthermic Perfusion.

Ann Surg Oncol. 2007 Feb;14(2):500-8. Epub 2006 Dec 6.
Baratti D, Kusamura S, Martinetti A, Seregni E, Oliva DG, Laterza B, Deraco M.
Department of Surgery, National Cancer Institute, Milan, Italy, marcello.deraco@istitutotumori.mi.it.

BACKGROUND: Recent phase I/II trials report encouraging results in selected patients with peritoneal mesothelioma (PM) treated with cytoreductive surgery (CRS) and intraperitoneal hyperthermic perfusion (IPHP). Circulating tumor markers have never been extensively investigated in the management of PM. We assessed the clinical role of markers in a large series of patients with PM undergoing CRS and IPHP. METHODS: Clinical data on 60 patients with PM operated with the intention to perform adequate CRS (residual tumor nodules <= 2.5mm) and IPHP were prospectively collected. Marker levels were determined pre-operatively, post-operatively, and routinely during long-term follow-up. Baseline diagnostic sensitivity, accuracy in monitoring response to treatment or tumor progression and prognostic significance were determined. RESULTS: Baseline diagnostic sensitivity was 53.3% for CA125, 0 for CEA, 3.8% for CA19.9 and 48.5% for CA15.3. Forty-six patients underwent adequate cytoreduction and IPHP; gross residual tumor was left after the operation in fourteen. Postoperatively, CA125 became negative in 21/22 patients with elevated baseline levels undergoing adequate CRS and IPHP, while remained elevated in 9/9 patients with persistent macroscopic disease. CA125 became positive in 12/12 patients with elevated baseline levels developing disease progression after adequate CRS and IPHP. Baseline CA125 showed borderline prognostic significance only among patients not previously treated with systemic chemotherapy. CONCLUSIONS: CA125 was elevated in the majority of patients with PM in the present series. yasak maker measurements paralleled tumor growth or regression after CRS and IPHP, suggesting the need of further studies to assess the role of CA125 in this clinical setting.

The role of PET in the surgical management of malignant pleural mesothelioma.

Lung Cancer. 2005 Jul;49 Suppl 1:S27-32. Epub 2005 Apr 14.
Flores RM.
Thoracic Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Room C-879, New York, NY 10021, USA. floresr@mskcc.org

Current imaging modalities fail to define precisely the extent of disease in MPM and are inaccurate in selecting patients for treatment. Previous studies have shown that CT and MRI provide anatomical information that is often imprecise in the preoperative staging of MPM. Consequently, about 25% of patients are found to have unresectable tumor at the time of exploratory thoracotomy. PET is now widely recognized as an important staging modality in many cancers, and PET SUV is reported as a prognostic indicator in several malignancies. However, only a few previous studies have investigated the utility of FDG PET scan in MPM. From 1998 to 2003, 65 patients with MPM underwent PET scans. Median PET SUV in the primary tumor was 6.6 (range, 2-23). The median follow-up for all surviving patients was 16 months. Median survivals were 14 and 24 months for the high and low SUV groups, respectively. In a multivariable analysis, high SUV tumors were associated with a 3.3 times greater risk of death than low SUV tumors (p = 0.03). Mixed histology carried a 3.2 times greater risk of death than epithelial histology (p = 0.03). SUV of >4 and mixed histology are poor risk factors in malignant pleural mesothelioma. These findings suggest that FDG-PET can be used to stratify patients for treatment and clinical trials.

PMID: 15950796 [PubMed - indexed for MEDLINE]

Factors influencing the outcome of radiotherapy in malignant mesothelioma of the pleura - a single-institution experience with 189 patients.

Int J Radiat Oncol Biol Phys 1999 Feb 1;43(3):511-6
de Graaf-Strukowska L, van der Zee J, van Putten W, Senan S
Department of Radiation Oncology, Daniel den Hoed Cancer Center/University Hospital Rotterdam, The Netherlands.

PURPOSE: To determine the factors influencing the response to palliative radiotherapy 9RT) in malignant mesothelioma of the pleura (MM).

METHODS AND MATERIALS: A retrospective review was conducted of the records of all patients with mesothelioma who were referred to our institution between 1979 and 1996. A total of 227 RT series were administered to 189 patients with MM. Of these, 21 patients with chest wall nodules also received concomitant local hyperthermia.

RESULTS: The median survival was 5 months from the start of RT and only 17% of patients were alive at 1 year after treatment. Chest pain and painful chest wall metastases were the main indications for RT. A higher local response rate was seen for patients treated with a 4-Gy per fraction scheme, vs. those receiving fractions of less than 4 Gy (50% vs. 39%). Pain recurrence occurred predominantly within the previous RT field, and pain recurred after a median of 69 days (range 32-363) in the group treated using 4-Gy fractions. When compared with a matched group, patients treated with combined RT and hyperthermia had higher response rates and fewer in-field recurrences.

CONCLUSIONS: RT provides local palliation in at least 50% of patients with MM who were treated using a 4-Gy/fraction scheme to a media dose of 36 Gy. The low response rates with RT alone suggest that combined RT and local hyperthermia should be further evaluated in MM.

PMID: 10078630, UI: 99176516

Results of a phase II trial of combined chemotherapy for patients with diffuse malignant mesothelioma of the pleura.

Cancer 1999 Apr 15;85(8):1740-9
Kasseyet S, Astoul P, Boutin C
Department of Pulmonology, University Hospital la Conception, Mediterranean University Medical School, Marseille, France.

BACKGROUND: Malignant pleural mesothelioma is associated with a poor prognosis because of its resistance to treatment. The authors conducted a Phase II trial in which two drugs (etoposide and 5-fluorouracil) were added to the Cancer and Leukemia Group B cisplatin-mitomycin regimen in an effort to define a more effective chemotherapy.

METHODS: Forty-five patients with confirmed Stage II malignant mesothelioma were prospectively enrolled in the study. Thirty-one patients received cisplatin 60 mg/m2 on Day 1, 5-fluorouracil 600 mg on Days 1-4, folinic acid 100 mg/m2 on Days 1-4, mitomycin C 10 mg/m2 on Day 3, and etoposide 100 mg/m2 i.v. on Days 1-3, with prophylactic hematopoietic growth factors. Fourteen patients received cisplatin, 5-fluorouracil, folinic acid, and mitomycin C with the protocol unchanged, and oral etoposide 50 mg on Days 1-21 without growth factors (1 cycle every 28 days). Histology included epithelial (in 33 cases), sacromatous (in 6), mixed (in 3), and unspecified type (in 3).

RESULTS: Two hundred eleven cycles were administered. Treatment was well tolerated and the major toxicity was hematologic: anemia in 30% of cases, neutropenia in 24%, and 2 probable cases of mitomycin-induced pneumonitis. The objective response rate was 38% (17 of 45 were partial responses), and the median response duration was 12 months. The median survival time was 16 months. There were no differences in response or survival between the 31 patients treated with growth factors and the 14 patients treated without them. Survival was slightly better for responders than for nonresponders who had stable disease or progression (20 vs. 10 months, P<0.05).

CONCLUSIONS: This four-drug combination was effective, with a notably high response rate, acceptable toxicity, and good adherence to protocol doses. The impact on survival was limited.

Systemic drug therapy of malignant pleural mesothelioma.

Monaldi Arch Chest Dis 1998 Apr;53(2):236-40
Ardizzoni A, Grossi F, Pennucci MC
Istituto Nazionale per la Ricerca sul Cancro, Division of Medical Oncology I, Genova, Italy.

Malignant pleural mesothelioma (MPM) is an uncommon malignancy characterized by a rapid clinical course. Few patients are possible candidates for radical surgery. According to most reviews, radiotherapy has a limited role in the treatment of MPM. The role of chemotherapy in the management of pleural mesothelioma still remains uncertain. The available data indicate that although 10-20% of patients are known to achieve on objective response to a number of chemotherapeutic agents, the impact on survival appears limited and improvement in the quality of life remains uncertain. The results of combination chemotherapy are comparable to those of single-agent chemotherapy and no major difference is detectable among the various combinations. Prospective phase II trials are recommended for the identification of new active treatments while large-scale randomized phase III trials are needed to identify the best available treatment. In addition, new standard criteria for eligibility and response assessment are required. This paper reviews the available literature on the systemic drug therapy of MPM.

Management of Mesothelioma By Neoadjuvant Chemotherapy, Followed by Resection and Radiation - A New Approach

    * George Haasler, M.D., Associate Professor, Surgery (Cardiothoracic), Medical College of Wisconsin;
    * Paul Ritch, M.D., Professor of Medicine (Hematology/Oncology);
    * J. Frank Wilson, M.D., F.A.C.R., Chairman, Radiation Oncology.

A 38-year-old man presented with progressive shortness of breath and right chest pain. He had been a non-smoker and was generally healthy. His employment history included some work as a roofer in his late teens. As an adult, he is a graphic artist. He has no known asbestos exposure.

Chest X-ray revealed a large right pleural effusion. Thoracentesis revealed mesothelial cells. Diagnostic thoracoscopy demonstrated an epithelial neoplasm consistent with mesothelioma of the epithelial type. The initial CT scan demonstrated a large tumor that involved the entire parietal pleura and appeared to extend across the midline, invading the thymic fat and the peri-esophageal region. Subcarinal lymph nodes were enlarged. We thought this tumor to be unresectable, and recommended pre-surgical treatment of the patient with chemotherapy, rather than to commit him to palliative options only. Although the usual aggressive multi-modality treatment for mesothelioma has involved initial resection followed by radiation and chemotherapy, we had seen neoadjuvant chemotherapy be helpful one other time with substantial success.

The patient underwent nine cycles of Adriamycin and Taxol chemotherapy, which he tolerated well. By that time, his tumor had decreased in size substantially to the point where his mediastinal disease appeared much more approachable. He underwent a standard pleural pneumonectomy, involving removal of the right lung, associated parietal pleura, right aspect of the pericardium and phrenic nerve, and the diaphragm. Reconstruction was carried out with a large Gortex patch tented across the lower chest to reconstruct the right hemidiaphragm. A second patch was placed along the right side of the pericardium. His postoperative course was somewhat stormy, with short-term renal failure requiring dialysis, some initial ventilatory insufficiency, and significant depression. After his discharge from the hospital, he underwent consolidative radiation therapy from which he recovered uneventfully. He has had no evidence of recurrence over one year following resection.

While this is still short-term information, this young man has done extremely well to date. Mesothelioma is a very unusual tumor to begin with, but in young people is even more rare. It usually presents in one of two histologic variants, or some combination- epithelial or mesenchymal. Patients with epithelial variants of these tumors are more likely to respond to treatments with reasonable prognosis. This history of asbestos exposure may be very distant, or even absent. While some of the best results that have been reported are those with radical surgery followed by chemotherapy and radiation therapy, this approach of neoadjuvant chemotherapy appears to have some promise for tumors that initially appear unresectable, especially with newer agents that may have increased activity against these tumors. The options for what to do depend significantly upon a patient's overall clinical state. For those in whom complete resection is not possible, palliative pleurectomy without pneumonectomy may nevertheless allow control of the pleural effusion and a marked reduction of the amount of tumor. In some instances, pleurectomy has been shown to extend survival. While always a challenging tumor, and one which often presents in debilitated patients, it is important to be aware of changes in both the palliative and potentially curative options for this disease.


Cisplatin is a chemotherapy drug that was approved by the Federal Drug Administration (FDA) in 1978 and is used to treat patients suffering from malignant pleural mesothelioma. Cisplatin is administered when surgical procedures are not an option, and it is often used in combination with other chemotherapy drugs, including Alimta. Manufactured by Bristol Myers Squibb, Cisplatin is also used to treat ovarian and lung cancer and is a highly effective method of mesothelioma treatment that is often recommended by oncologists.

Cisplatin is administered intravenously and may be given along with other drugs, such as anti-nausea medication and antibiotics that prevent buildup of Cisplatin within the kidneys. Your doctor will determine how often you receive Cisplatin and for how long, but patients who receive Cisplatin in tandem with Alimta will follow a 21-day treatment cycle.

Because Cisplatin was developed three decades ago, the side effects associated with this drug are often much more severe. Side effects include damage to the kidneys, (which is often prevented by administering other drugs, such as a diuretic or sodium polystyrene sulfonate, during Cisplatin treatment) serious nausea, depleted levels of calcium, potassium and other nutrients, loss of appetite, tiredness, hair loss, and an increased risk of infection. Because cancer treatment in general has become so advanced since Cisplatin was first developed, doctors are generally able to control the unpleasant side effects associated with Cisplatin treatment in an effort to make the patient more comfortable.

Other drugs similar to Cisplatin include Carboplatin, generally used to treat cancer of the lung, head and neck, and Oxaliplatin, which is most often used to treat colorectal cancer.

As with any mesothelioma cancer drug, your doctor will decide whether or not Cisplatin is a beneficial option for treating your cancer.
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