Mesothelioma (cancer of the mesothelium) is a disease in which cells of the mesothelium become abnormal and divide without control or order. They can invade and damage nearby tissues and organs. Cancer cells can also metastasize (spread) from their original site to other parts of the body. Most cases of mesothelioma begin in the pleura or peritoneum.
Mesothelioma is a rare form of cancer in which malignant (cancerous) cells are found in the mesothelium, a protective sac that covers most of the body's internal organs. Most people who develop mesothelioma have worked on jobs where they inhaled asbestos particles.
Source: National Cancer Institute
Mesothelioma Chemotherapy
Chemotherapy is the only treatment for mesothelioma that has been proven to improve survival in randomised and controlled trials. The landmark study published in 2003 by Vogelzang and colleagues compared cisplatin chemotherapy alone with a combination of cisplatin and pemetrexed (brand name Alimta) chemotherapy) in patients who had not received chemotherapy for malignant pleural mesothelioma previously and were not candidates for more aggressive "curative" surgery. This trial was the first to report a survival advantage from chemotherapy in malignant pleural mesothelioma, showing a statistically significant improvement in median survival from 10 months in the patients treated with cisplatin alone to 13.3 months in the combination pemetrexed group in patients who received supplementation with folate and vitamin B12. Vitamin supplementation was given to most patients in the trial and pemetrexed related side effects were significantly less in patients receiving pemetrexed when they also received daily oral folate 500mcg and intramuscular vitamin B12 1000mcg every 9 weeks compared with patients receiving pemetrexed without vitamin supplementation. The objective response rate increased from 20% in the cisplatin group to 46% in the combination pemetrexed group. Some side effects such as nausea and vomiting, stomatitis, and diarrhoea were more common in the combination pemetrexed group but only affected a minority of patients and overall the combination of pemetrexed and cisplatin was well tolerated when patients received vitamin supplementation; both quality of life and lung function tests improved in the combination pemetrexed group. In February 2004, the United States Food and Drug Administration approved pemetrexed for treatment of malignant pleural mesothelioma. However, there are still unanswered questions about the optimal use of chemotherapy, including when to start treatment, and the optimal number of cycles to give.
Cisplatin in combination with raltitrexed has shown an improvement in survival similar to that reported for pemetrexed in combination with cisplatin, but raltitrexed is no longer commercially available for this indication. For patients unable to tolerate pemetrexed, cisplatin in combination with gemcitabine or vinorelbine is an alternative, or vinorelbine on its own, although a survival benefit has not been shown for these drugs. For patients in whom cisplatin cannot be used, carboplatin can be substituted but non-randomised data have shown lower response rates and high rates of haematological toxicity for carboplatin-based combinations, albeit with similar survival figures to patients receiving cisplatin.
In January 2009, the United States FDA approved using conventional therapies such as surgery in combination with radiation and or chemotherapy on stage I or II Mesothelioma after research conducted by a nationwide study by Duke University concluded an almost 50 point increase in remission rates.
http://en.wikipedia.org/wiki/Mesothelioma
Cisplatin in combination with raltitrexed has shown an improvement in survival similar to that reported for pemetrexed in combination with cisplatin, but raltitrexed is no longer commercially available for this indication. For patients unable to tolerate pemetrexed, cisplatin in combination with gemcitabine or vinorelbine is an alternative, or vinorelbine on its own, although a survival benefit has not been shown for these drugs. For patients in whom cisplatin cannot be used, carboplatin can be substituted but non-randomised data have shown lower response rates and high rates of haematological toxicity for carboplatin-based combinations, albeit with similar survival figures to patients receiving cisplatin.
In January 2009, the United States FDA approved using conventional therapies such as surgery in combination with radiation and or chemotherapy on stage I or II Mesothelioma after research conducted by a nationwide study by Duke University concluded an almost 50 point increase in remission rates.
http://en.wikipedia.org/wiki/Mesothelioma
Radiation treatment
For patients with localized disease, and who can tolerate a radical surgery, radiation is often given post-operatively as a consolidative treatment. The entire hemi-thorax is treated with radiation therapy, often given simultaneously with chemotherapy. This approach of using surgery followed by radiation with chemotherapy has been pioneered by the thoracic oncology team at Brigham & Women's Hospital in Boston. Delivering radiation and chemotherapy after a radical surgery has led to extended life expectancy in selected patient populations with some patients surviving more than 5 years. As part of a curative approach to mesothelioma, radiotherapy is also commonly applied to the sites of chest drain insertion, in order to prevent growth of the tumor along the track in the chest wall.
Although mesothelioma is generally resistant to curative treatment with radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of a major blood vessel. Radiation therapy when given alone with curative intent has never been shown to improve survival from mesothelioma. The necessary radiation dose to treat mesothelioma that has not been surgically removed would be very toxic.
Although mesothelioma is generally resistant to curative treatment with radiotherapy alone, palliative treatment regimens are sometimes used to relieve symptoms arising from tumor growth, such as obstruction of a major blood vessel. Radiation therapy when given alone with curative intent has never been shown to improve survival from mesothelioma. The necessary radiation dose to treat mesothelioma that has not been surgically removed would be very toxic.
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Radiation treatment
Heated Intraoperative Intraperitoneal Chemotherapy
Heated Intraoperative Intraperitoneal Chemotherapy
A procedure known as heated intraoperative intraperitoneal chemotherapy was developed by Paul Sugarbaker at the Washington Cancer Institute.The surgeon removes as much of the tumor as possible followed by the direct administration of a chemotherapy agent, heated to between 40 and 48°C, in the abdomen. The fluid is perfused for 60 to 120 minutes and then drained.
This technique permits the administration of high concentrations of selected drugs into the abdominal and pelvic surfaces. Heating the chemotherapy treatment increases the penetration of the drugs into tissues. Also, heating itself damages the malignant cells more than the normal cells.
surse: http://en.wikipedia.org/wiki/Mesothelioma
Coliseum Technique for Hyperthermic Intraoperative Intraperitoneal Chemotherapy
Cytoreductive surgery was attempted to make each patient macroscopically disease-free. At the end of the procedure, four closed suction catheters (Zimmer Inc, Warsaw, IN) were placed through the abdominal wall, using stab incisions, to lie beneath each hemidiaphragm and two within the pelvis (Figure 2). A Tenckhoff catheter (Quinton Inc, Seattle, WA) was placed through the abdominal wall if early postoperative intraperitoneal chemotherapy (EPIC) is planned. Otherwise, the Tenckhoff catheter was placed over the midline abdominal incision for use in HIIC. The Tenckhoff catheter functioned as an in-flow line. The closed suction catheters were used as drainage lines for intraoperative lavage and remained in place for postoperative abdominal drainage. Two temperature probes (Respiratory Support Products Inc. Irvine, CA) were then placed over the edge of the abdominal incision. One temperature probe was tied to the Tenckhoff catheter. The other temperature probe was tied to a closed suction drain at a distant location from the Tenckhoff. All transabdominal tubes were secured to the skin and to the peritoneum with purse string sutures to prevent fluid leakage. The Thompson retractor (Thompson Surgical Instruments, Traverse City, MI) was then repositioned as in Figure 2. The abdomen was left open with the skin edges suspended to the Thompson retractor with a number 2 running nylon suture. To prevent spillage of the chemotherapy and to control potential chemotherapy vapors, a plastic sheet was sutured to the wound edges. A slit incision was then made in the center of the plastic sheet to allow the surgeon access to all intraabdominal surfaces and to manually control the fluid distribution. After the hyperthermic perfusion was complete, bowel anastomoses and other reconstructive procedures were performed.
The hyperthermic perfusion with mitomycin C was carried out for ninety minutes using a HIIC custom tubing pack (Bard Cardiology, Haverhill, MA), two cardiopulmonary bypass pumps (Travenol Labs, Morton Grove, IL) and a Sarns heater/cooler unit (3M Cardiovascular Systems, Ann Arbor, MI). Three liters of 1.5% dextrose peritoneal dialysis solution containing the appropriate cytotoxic drug(s) were heated and infused at approximately 1 liter per minute into the abdominal cavity. The perfusate was heated to approximately 43oC. Temperatures were measured with a Labcraft digital thermometer (Curtin Matheson Scientific, Jessup, MD). The temperature at the In-Flow line was approximately 44oC. The Tenckhoff temperature probe was maintained between 42 and 43oC. The temperature probes and all temporary 3-0 chromic sutures were removed at the end of the hyperthermic perfusion.
Urine output was monitored by the anesthesiologist. At his or her discretion fluid challenge, furosemide, renal dose dopamine or mannitol were instituted to maintain a brisk diuresis. Urine output was measured every 15 minutes. It was maintained at greater than 400 cc per hour during the ninety minutes of the hyperthermic perfusion and for one hour thereafter.
In addition to intraoperative hyperthermic perfusion, patients with high grade tumor or incomplete cytoreduction received five days of early postoperative intraperitoneal chemotherapy. These five days of chemotherapy were given on postoperative days 1-5. Each dose was prepared in 1000 to 2000 cc of 1.5% dextrose peritoneal dialysis solution, depending on body size. Each dose was infused as quickly as possible, allowed to dwell for 23 hours then drained for one hour prior to the next infusion.
Levels of 5-FU were monitored in the peritoneal fluid and plasma of 9 patients on the first postoperative day. Three patients received cytoreductive surgery, HIIC and early postoperative 5-FU. Six patients received only cytoreduction and early postoperative 5-FU. Samples were obtained at regular intervals from 0 to 180 minutes post infusion.
Drug doses were as follows:
For pseudomyxoma peritonei and adenocarcinoma from appendiceal, colonic and rectal cancer:
| Drug | Day | Route | Dose |
| Mitomycin C | 0 | IP | 12.5 mg/m2 (max. 25 mg) for males or 10.0 mg/m2 (max 20 mg) for females in 3 liters. |
| 5-Fluorouracil | 1-5 | IP | 15 mg/m2 x 5 days |
For gastric, pancreatic and ovarian cancer, mesothelioma, and sarcoma:
| Drug | Day | Route | Dose |
| Cisplatin | 0 | IP | 50 mg/m2 (max. 100 mg) |
| Doxorubicin | 0 | IP | 50 mg/m2 (max. 100 mg) |
| Mitomycin C | 0 | IP | 7 mg/m2 (max. 14 mg) |
| Doxorubicin | 1-5 | IP | 15 mg/m2 x 5 days |
Standardized dose reductions occurred as follows:
33% dose reduction for age > 65 years
33% dose reduction for patients with compromised renal function.
50% dose reduction for prior exposure to heavy chemotherapy or radiation therapy
Other dose reductions as deemed necessary by the Principal Investigator.
For patients undergoing pharmacokinetic monitoring, samples of plasma, urine and perfusate were obtained at fifteen minute intervals during the hyperthermic perfusion and at the end of the procedure. These measurements were used for pharmacokinetic calculations and to help relate possible complications to systemic and intraperitoneal drug levels.
Patients were monitored for complications associated with intraperitoneal hyperthermia including: enteral complications (fistulas, anastomotic leaks), wound complications (pancreatitis, bile leaks, wound dehiscence), hematologic toxicities, prolonged ileus and line sepsis.
surse: http://www.surgicaloncology.com/hiicman.htm
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