Dickgreber NJ, Fink TH, Latz JE, Hossain AM, Musib LC, Thomas M.

Hannover Medical School, Hannover, Germany. nicolas.dickgreber@gmx.de

Abstract

Purpose: Pemetrexed is approved as monotherapy and in combination with cisplatin. The established combination dose was identified before the addition of folic acid and vitamin B₁₂ to the treatment regimen. We evaluated the toxicity and pharmacokinetics (PK) of higher pemetrexed doses with cisplatin and vitamin supplementation.

Experimental Design: Patients with malignant pleural mesothelioma or non–small cell lung cancer received pemetrexed doses from 500 to 900 mg/m² + 75 mg/m² cisplatin once every 21 days. Folic acid and vitamin B₁₂ were administered per label recommendations.

Results: Twenty-one patients received a combined total of 84 cycles. The maximum tolerated dose was 900 mg/m² pemetrexed + 75 mg/m² cisplatin. Dose-limiting toxicities at this dose included grade 3 anemia, bronchopneumonia, and neutropenia, and 1 death from sepsis secondary to grade 4 febrile neutropenia, considered possibly related to study drugs. The recommended dose was 800 mg/m² pemetrexed + 75 mg/m² cisplatin. Pemetrexed PK were consistent across doses; pemetrexed did not seem to affect total or free platinum PK.

Conclusions: Pemetrexed with vitamin supplementation was safe and well tolerated at higher doses than the currently established 500 mg/m² + 75 mg/m² cisplatin. Based on this study, the recommended dose would be 800 mg/m² pemetrexed + 75 mg/m² cisplatin. However, recent studies showed a lack of improved efficacy for 900 or 1,000 mg/m² single-agent pemetrexed versus 500 mg/m² and a lack of PK/pharmacodynamic exposure-response relationship for the pemetrexed/cisplatin combination across pemetrexed exposures corresponding to this dose range. Based on currently available evidence, we recommend retaining the established dose.

Glossary

regimen

(rej-uh-men) a strict, regulated plan (such as diet, exercise, or other activity) designed to reach certain goals. In cancer treatment, a plan to treat cancer.

grade

The grade of a cancer reflects how abnormal it looks under the microscope. There are several grading systems for cancer, such as the Gleason score for prostate cancer. Each grading system divides cancer into those with the greatest abnormality (poorly differentiated), the least abnormality (well-differentiated), and those in between (moderately differentiated). Grading is done by the pathologist who examines the tissue from the biopsy. It is important because higher grade cancers tend to grow and spread more quickly and have a worse prognosis.

cell

the basic unit of which all living things are made. Cells replace themselves by splitting and forming new cells (mitosis). The processes that control the formation of new cells and the death of old cells are disrupted in cancer.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

anemia

(uh-neem-ee-uh) low red blood cell count.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

pemetrexed

chemotheraputic agent that interferes with a crucial process that allows cancer cells to reproduce and spread. Specifically, pemetrexed stops the production of three enzymes that are required to feed the cancer cell. Often used in combination with cisplatin. Marketed under the name ALIMTA. See: Alimta.

Xanthopoulos A, Bauer TT, Blum TG, Kollmeier J, Schönfeld N, Serke M.

Respiratory Diseases Clinic Heckeshorn, Department of Pneumology, HELIOS Klinikum Emil von Behring, Berlin, Germany. torsten.bauer@helios-kliniken.de.

Abstract

Background: The aim of this study was to investigate the efficacy and safety of oxaliplatin +/- gemcitabine in patients with diffuse malignant pleural mesothelioma (MPM) pretreated with pemetrexed.

Methods: The study enrolled consecutive patients with relapsed MPM, all of them pretreated with a platin-pemetrexed-based chemotherapy. Oxaliplatin 80 mg/m2 was administered as monotherapy or in combination with gemcitabine 1000 mg/m2 given on day 1 and 8. Cycles were repeated every 21 days. The primary endpoints were response rate and disease control rate. Secondary endpoints included overall survival (OS), time to tumour progression (TTP), progression-free survival (PFS), time to treatment failure (TTF), and toxicity.

Results: Between February 2005 and September 2007 29 patients (median age: 65.0 years, World Health Organisation (WHO) performance status: 0-3) were enrolled. The follow-up period encompassed 5.4 to 97.4 weeks (median: 24.3 weeks). Out of these 29 patients, 15 were treated in second, 10 in third, 3 in fourth and 1 in fifth line, respectively. The majority of the patients received the combination oxaliplatin and gemcitabine (n = 25 vs. 4; 86.2 vs. 13.8%).The median overall survival (OS) was 71.7 weeks (30.6-243.3 weeks), whereas survival from the start of oxaliplatin/gemcitabine-treatment was 24.3 weeks (5.4-97.3 weeks). Median time to tumour progression (TTP) was 9.3 weeks (3.0-67.6 weeks).Partial response (PR) was observed in 2 patients (6.9%), stable disease (SD) for at least three courses of treatment in 11 patients (37.9%). Thus, disease control rate was 44.8%, whereas 16 of 29 patients exhibited progressive disease (55.2%).The toxicity profile was favourable, with no WHO grade 4-toxicities, only few dose-reductions were performed due to non-symptomatic haematotoxicities (neutropenia, thrombopenia). Mild WHO grade 2 neurotoxicity was seen in 6 patients.

Conclusion: Pemetrexed-pretreated patients with progressive MPM may benefit from a consecutive chemotherapy with oxaliplatin and gemcitabine without significant toxicity.

Glossary

grade

The grade of a cancer reflects how abnormal it looks under the microscope. There are several grading systems for cancer, such as the Gleason score for prostate cancer. Each grading system divides cancer into those with the greatest abnormality (poorly differentiated), the least abnormality (well-differentiated), and those in between (moderately differentiated). Grading is done by the pathologist who examines the tissue from the biopsy. It is important because higher grade cancers tend to grow and spread more quickly and have a worse prognosis.

chemotherapy

(key-mo-THER-uh-pee) treatment with drugs to destroy cancer cells. Chemotherapy is often used with surgery or radiation to treat cancer when the cancer has spread, when it has come back (recurred), or when there is a strong chance that it could recur.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

pemetrexed

chemotheraputic agent that interferes with a crucial process that allows cancer cells to reproduce and spread. Specifically, pemetrexed stops the production of three enzymes that are required to feed the cancer cell. Often used in combination with cisplatin. Marketed under the name ALIMTA. See: Alimta.

Carteni G, Manegold C, Garcia GM, Siena S, Zielinski CC, Amadori D, Liu Y, Blatter J, Visseren-Grul C, Stahel R.

Cardarelli Hospital, Medical Oncology, Via Cardarelli 9, 80100 Naples, Italy. giacomo.carteni@ospedalecardarelli.it

Abstract

Aim: Peritoneal mesothelioma (PM) has rarely been studied. The Expanded Access Program (EAP) provided access to 109 patients with PM.

Methods: This was a nonrandomized, open-label study conducted in chemo-naïve or previously treated patients with PM not amenable to curative surgery. Patients received pemetrexed (PEM) 500mg/m2 alone or with cisplatin (CIS) 75mg/m2 or carboplatin (CARBO) AUC 5 every 21 days, supplemented with standard vitamin B12, folate, and dexamethasone.

Results: Response rates (95% CI) for PEM, PEM/CIS, and PEM/CARBO were 12.5% (3.5, 29.0), 20.0% (7.7, 38.6), and 24.1% (10.3, 43.5), respectively. Median survival for PEM was 10.3 months. One-year survival rates for PEM/CIS and PEM were 57.4% (95% CI: 10.3, 100) and 41.5% (95% CI: 4.6, 78.4), respectively, and were not available for PEM/CARBO. Anemia was the most common serious adverse event (6.4%). Neutropenia (34.6%) was the most frequent CTC grade 3 or 4 toxicity reported.

Concluding statement: PEM with or without a platinum agent was both active and well tolerated in patients with peritoneal mesothelioma.

Keywords: Peritoneal mesothelioma, Pemetrexed, Platinum, Cisplatin, Carboplatin, Compassionate-use program, Expanded Access Program (EAP).

Glossary

oncology

(on-call-o-jee) the branch of medicine concerned with the diagnosis and treatment of cancer.

grade

The grade of a cancer reflects how abnormal it looks under the microscope. There are several grading systems for cancer, such as the Gleason score for prostate cancer. Each grading system divides cancer into those with the greatest abnormality (poorly differentiated), the least abnormality (well-differentiated), and those in between (moderately differentiated). Grading is done by the pathologist who examines the tissue from the biopsy. It is important because higher grade cancers tend to grow and spread more quickly and have a worse prognosis.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

anemia

(uh-neem-ee-uh) low red blood cell count.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

peritoneal

(pair-uh-tuh-nee-al) the serous membrane that lines the cavity of the abdomen. (More on Peritoneal Mesothelioma.)

pemetrexed

chemotheraputic agent that interferes with a crucial process that allows cancer cells to reproduce and spread. Specifically, pemetrexed stops the production of three enzymes that are required to feed the cancer cell. Often used in combination with cisplatin. Marketed under the name ALIMTA. See: Alimta.

Berghmans T.

Département des Soins Intensifs et Oncologie Thoracique, Institut Jules-Bordet (Centre des Tumeurs de l’Université Libre de Bruxelles), 1 Rue Héger-Bordet, Brussels, Belgium. thierry.berghmanns@bordet.be

Abstract

Malignant pleural mesothelioma is a rare tumour of poor prognosis. Available therapeutics have restricted efficacy. Pleuro-pneumonectomy is the only treatment with curative intent but it could be offered to a limited and well selected group of patients. The role of radiotherapy is palliative and its preventive role on malignant seeding after invasive procedures is controversial. There are few active cytotoxic drugs in this disease. Currently, based on two randomised trials, the most efficacious chemotherapy regimen consists in a combination of cisplatin and an antifolate agent, pemetrexed or raltitrexed.

Keywords: Mesothelioma, Surgery, Radiotherapy, Chemotherapy

Glossary

regimen

(rej-uh-men) a strict, regulated plan (such as diet, exercise, or other activity) designed to reach certain goals. In cancer treatment, a plan to treat cancer.

prognosis

(prog-no-sis) a prediction of the course of disease; the outlook for the cure of the patient. For example, women with breast cancer that was detected early and who received prompt treatment have a good prognosis.

cytotoxic

(site-o-tox-ik) toxic to cells; cell-killing.

DES

abbreviation for diethylstilbestrola (die-eth-l-steh-BES-ter-ol),  synthetic form of estrogen.

chemotherapy

(key-mo-THER-uh-pee) treatment with drugs to destroy cancer cells. Chemotherapy is often used with surgery or radiation to treat cancer when the cancer has spread, when it has come back (recurred), or when there is a strong chance that it could recur.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

pemetrexed

chemotheraputic agent that interferes with a crucial process that allows cancer cells to reproduce and spread. Specifically, pemetrexed stops the production of three enzymes that are required to feed the cancer cell. Often used in combination with cisplatin. Marketed under the name ALIMTA. See: Alimta.

Saito Y, Furukawa T, Arano Y, Fujibayashi Y, Saga T.

Molecular Imaging Center, National Institute of Radiological Sciences, Chiba, 263-8555, Japan.

Abstract

Introduction: Various techniques are available for in vivo imaging, and precise understanding of their characteristics is essential for effective use of the imaging results. We established human mesothelioma cell lines expressing red fluorescent protein (RFP) and examined their fluorescence intensity and uptake of positron emission tomography (PET) tracer analogs to compare their characteristics and assess their usefulness in the evaluation of therapeutics.

Method: A human mesothelioma cell line was stably transfected to express RFP. Fluorescence, cell number and protein amount were measured during cell growth and treatment with cytotoxic reagents. In in vivo experiments, RFP-expressing cells were injected subcutaneously or into the pleural cavity of nude mice, and fluorescence images were taken with or without pemetrexed treatment. The uptake of [³H]3′-deoxy-3′-fluorothymidine ([³H]FLT) and [¹⁴C]2-fluoro-2-deoxy-d-glucose ([¹⁴C]FDG) under treatment with the above reagents in vitro and in vivo were examined.

Results: Strong correlation was observed between fluorescence intensity and total cell number with or without cytotoxic treatment. The uptake of [³H]FLT and [¹⁴C]FDG decreased rapidly after the initiation of treatment with actinomycin D or cycloheximide. When treated with pemetrexed, the uptake of [³H]FLT temporarily increased. The cells formed subcutaneous and orthotopic tumors, with fluorescence intensity correlating with tumor volume. The correlation was sustained under pemetrexed treatment. The uptake of [³H]FLT in vivo increased significantly early after pemetrexed treatment.

Conclusion: Fluorescence imaging could be used to semiquantitatively monitor tumor size, whereas PET could be used to monitor tumor response to therapeutic treatments, and especially, FLT might be a good marker of the response to anti-folate chemotherapeutics.

Keywords: Mesothelioma; Mouse tumor model; Fluorescence imaging; PET; FLT

Glossary

imaging

any method used to produce a picture of internal body structures. Some imaging methods used to detect cancer are x-rays (including mammograms and CT scans), magnetic resonance imaging (MRI), scintigraphy, and ultrasound.

cytotoxic

(site-o-tox-ik) toxic to cells; cell-killing.

cell

the basic unit of which all living things are made. Cells replace themselves by splitting and forming new cells (mitosis). The processes that control the formation of new cells and the death of old cells are disrupted in cancer.

tumor

an abnormal lump or mass of tissue. Tumors can be benign (not cancerous) or malignant (cancerous).

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

pemetrexed

chemotheraputic agent that interferes with a crucial process that allows cancer cells to reproduce and spread. Specifically, pemetrexed stops the production of three enzymes that are required to feed the cancer cell. Often used in combination with cisplatin. Marketed under the name ALIMTA. See: Alimta.

Lee CW, Murray N, Anderson H, Rao SC, Bishop W.

BC Cancer Agency – Fraser Valley Centre, 13750 96th Avenue, Surrey, British Columbia, Canada V3V 1Z2. clee@bccancer.bc.ca

Abstract

Cisplatin plus pemetrexed has been standard systemic therapy for malignant pleural mesothelioma (MPM) since the landmark randomized trial reported in 2003. However, the combination of cisplatin and gemcitabine was incorporated into clinical practice following publication of promising phase II trial results in 1999. The impact of these platinum-based regimens is assessed in this review of practice in the province of British Columbia. All cases of MPM diagnosed from 1999 to 2005 were identified in a provincial registry using ICD-O codes. The clinical records of individuals referred to the BC Cancer Agency were reviewed, and those treated with a platinum analog plus gemcitabine or pemetrexed as first-line therapy were included in survival analyses. During the selected period, 81 patients were treated first-line with a platinum analog plus gemcitabine (n=40) or pemetrexed (n=41). Characteristics of the entire cohort include: age at diagnosis, mean 65 years (median 66, range 43-84); gender, male 70 (86%); laterality of disease, right-sided 51 (63%); histology, epithelioid or not otherwise specified 69 (85%). Median survival was 10 months (95% confidence interval, 7.7-12.3), with 1- and 2-year survival rates 0.42 and 0.21, respectively. Survival did not appear to be influenced by the chemotherapy agent used. Survival outcomes with chemotherapy for MPM in the province are comparable to what is reported in the literature. No difference is seen combining platinum analogs with gemcitabine or pemetrexed. Platinum-based doublets might represent a therapeutic ceiling for cytotoxic chemotherapy in MPM.

Glossary

therapy

any of the measures taken to treat a disease. Unproven therapy is any therapy that has not been scientifically tested and approved. Use of an unproven therapy instead of standard (proven) therapy is called alternative therapy. Some alternative therapies have dangerous or even life-threatening side effects. For others, the main danger is that a patient may lose the opportunity to benefit from standard therapy. Complementary therapy, on the other hand, refers to therapies used in addition to standard therapy. Some complementary therapies may help relieve certain symptoms of cancer, relieve side effects of standard cancer therapy, or improve a patient's sense of well-being. The ACS recommends that patients considering use of any alternative or complementary therapy discuss this with their health care team.

systemic therapy

treatment that reaches and affects cells throughout the body; for example, chemotherapy.

diagnosis

identifying a disease by its signs or symptoms, and by using imaging procedures and laboratory findings. The earlier a diagnosis of cancer is made, the better the chance for long-term survival.

cytotoxic

(site-o-tox-ik) toxic to cells; cell-killing.

chemotherapy

(key-mo-THER-uh-pee) treatment with drugs to destroy cancer cells. Chemotherapy is often used with surgery or radiation to treat cancer when the cancer has spread, when it has come back (recurred), or when there is a strong chance that it could recur.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

pemetrexed

chemotheraputic agent that interferes with a crucial process that allows cancer cells to reproduce and spread. Specifically, pemetrexed stops the production of three enzymes that are required to feed the cancer cell. Often used in combination with cisplatin. Marketed under the name ALIMTA. See: Alimta.

Hanauske AR, Dumez H, Piccart M, Yilmaz E, Graefe T, Gil T, Simms L, Musib L, Awada A.

St. Georg Hospital, Ahrensburger Weg 129b, 22359, Hamburg, Germany, hanauskeax@lilly.com.

Abstract

The objectives of this phase I study were to determine the maximum tolerated dose (MTD), recommended phase II dose (RD), antitumor activity, safety, and pharmacokinetics of pemetrexed–paclitaxel combination. Patients (N = 95) with advanced solid tumors were assigned to three schedules (21-day cycles [q21d]). Starting doses for each schedule of pemetrexed and paclitaxel, respectively, were: (S1) 400 and 135 mg/m2 on d1; (S2) 400 mg/m2 d1 and 40 mg/m2 d1 and d8; S3) 400 mg/m2 d8 and 30 mg/m2 d1 and d8. MTD was 500/135 mg/m2 (S1), 400/40 mg/m2 (S2), and 500/120 mg/m2 (S3). Most common dose limiting toxicities were febrile neutropenia, fatigue, and neuromotor toxicities. Most common toxicity was grade 3/4 lymphopenia. Four patients had partial response, 43 patients had stable disease. The RD determined was pemetrexed 500 mg/m2 (d8) and paclitaxel 90 mg/m2 (d1 and d8), q21d. The combination was well tolerated and showed efficacy in thyroid carcinoma and mesothelioma.

Keywords: Pemetrexed – Paclitaxel – Phase I – Combination chemotherapy – Vitamin supplementation

Glossary

grade

The grade of a cancer reflects how abnormal it looks under the microscope. There are several grading systems for cancer, such as the Gleason score for prostate cancer. Each grading system divides cancer into those with the greatest abnormality (poorly differentiated), the least abnormality (well-differentiated), and those in between (moderately differentiated). Grading is done by the pathologist who examines the tissue from the biopsy. It is important because higher grade cancers tend to grow and spread more quickly and have a worse prognosis.

chemotherapy

(key-mo-THER-uh-pee) treatment with drugs to destroy cancer cells. Chemotherapy is often used with surgery or radiation to treat cancer when the cancer has spread, when it has come back (recurred), or when there is a strong chance that it could recur.

carcinoma

(car-sin-o-ma) a malignant tumor that begins in the lining layer (epithelial cells) of organs. At least 80% of all cancers are carcinomas.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

pemetrexed

chemotheraputic agent that interferes with a crucial process that allows cancer cells to reproduce and spread. Specifically, pemetrexed stops the production of three enzymes that are required to feed the cancer cell. Often used in combination with cisplatin. Marketed under the name ALIMTA. See: Alimta.

Li L, Razak AR, Hughes A.

Department of Medical Oncology, Northern Centre for Cancer Treatment (NCCT), Westgate Road, Newcastle upon Tyne NE4 6BE, United Kingdom.

Abstract

Background: Malignant pleural mesothelioma is an aggressive cancer. Chemotherapy with cisplatin and pemetrexed can improve overall survival but has a toxic profile. Substitution of cisplatin with carboplatin may avoid some potential side-effects. Therefore, we undertook a retrospective review to assess the effectiveness and tolerability of carboplatin and pemetrexed in patients with malignant pleural mesothelioma in clinical practice.

Methods: Patients with malignant pleural mesothelioma who had been treated with carboplatin and pemetrexed were retrospectively identified from pharmacy databases. The endpoints were disease control rate, time to treatment failure, clinical improvement rate and overall survival. We also evaluated any significant haematological and non-haematological toxicities.

Results: A total of 49 patients were identified. Of 45 evaluable cases, the disease control rate was achieved in 34 patients (69%, 95% CI 55–82, intention to treat analysis). The clinical response rate was achieved in 34 out of 49 patients (69%, 95% CI 55–82). The median time to treatment failure was 4.6 months (95% CI 3.4–5.8) and median overall survival was 14 months (95% CI 9.5–18.5). Grade 3/4 haematological toxicities were observed in 7 patients (14.3%). Grade 3/4 non-haematological toxicities were seen in 12 patients (24.5%). No toxic deaths were recorded.

Conclusion: The combination of carboplatin and pemetrexed may be a viable option in the treatment of malignant pleural mesothelioma.

Keywords: Pleural; Mesothelioma; Pemetrexed; Carboplatin; Chemotherapy; Disease control; Retrospective; Survival

Abbreviations: CI, confidence interval; MPM, malignant pleural mesothelioma; IMIG, International Mesothelioma Interest Group; AUC, area under the curve; i.v., intravenous; DCR, disease control rate; CT, computed tomography; TTF, time to treatment failure; OS, overall survival

Glossary

oncology

(on-call-o-jee) the branch of medicine concerned with the diagnosis and treatment of cancer.

grade

The grade of a cancer reflects how abnormal it looks under the microscope. There are several grading systems for cancer, such as the Gleason score for prostate cancer. Each grading system divides cancer into those with the greatest abnormality (poorly differentiated), the least abnormality (well-differentiated), and those in between (moderately differentiated). Grading is done by the pathologist who examines the tissue from the biopsy. It is important because higher grade cancers tend to grow and spread more quickly and have a worse prognosis.

chemotherapy

(key-mo-THER-uh-pee) treatment with drugs to destroy cancer cells. Chemotherapy is often used with surgery or radiation to treat cancer when the cancer has spread, when it has come back (recurred), or when there is a strong chance that it could recur.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

pemetrexed

chemotheraputic agent that interferes with a crucial process that allows cancer cells to reproduce and spread. Specifically, pemetrexed stops the production of three enzymes that are required to feed the cancer cell. Often used in combination with cisplatin. Marketed under the name ALIMTA. See: Alimta.

Hesdorffer ME, Chabot J, DeRosa C, Taub R.

Mesothelioma Applied Research Foundation, Santa Barbara, CA, USA. mhesdorer@curemeso.org

Abstract

Opinion statement: Malignant peritoneal mesothelioma (MPM) is an aggressive neoplasm that rapidly spreads within the confines of the abdominal cavity to involve most accessible peritoneal and omental surfaces. Current treatment options are unsatisfactory, and new approaches are needed. Recent publications have reported improved survival with an intensive loco-regional treatment strategy including cytoreductive surgery (CRS) along with hyperthermic intraperitoneal chemotherapy (HIPEC). We have noted at our institution prolonged survival in selected patients after intensive multimodality treatment. Our most recently reported trial included initial laparatomy with omentectomy, resection of peritoneal implants, and placement of bilateral peritoneal Portacath; repeated courses of intraperitoneal chemotherapy with doxorubicin, cisplatin, and interferon gamma; second-look laparotomy; and intraoperative hyperthermic perfusion with mitomycin and cisplatin, followed by whole abdominal radiation. To date there have been no universally accepted treatments for MPM. Unless referred to a specialty center, patients are routinely treated with pemetrexed and cisplatin which has been shown to increase survival in pleural mesothelioma.

Glossary

resection

surgery to remove part or all of an organ or other structure.

oncology

(on-call-o-jee) the branch of medicine concerned with the diagnosis and treatment of cancer.

neoplasm

(nee-o-plas-um) an abnormal growth (tumor) that starts from a single altered cell; a neoplasm may be benign or malignant. Cancer is a malignant neoplasm.

interferon

(in-ter-fear-on) a protein produced by cells. Interferon helps regulate the body's immune system, boosting activity when a threat, such as a virus, is found. Scientists have learned that interferon helps fight against cancer, so it is used to treat some types of cancer.

chemotherapy

(key-mo-THER-uh-pee) treatment with drugs to destroy cancer cells. Chemotherapy is often used with surgery or radiation to treat cancer when the cancer has spread, when it has come back (recurred), or when there is a strong chance that it could recur.

bilateral

(bi-lat-er-ul) on both sides of the body; for example, bilateral breast cancer is cancer in both breasts.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

peritoneal

(pair-uh-tuh-nee-al) the serous membrane that lines the cavity of the abdomen. (More on Peritoneal Mesothelioma.)

pemetrexed

chemotheraputic agent that interferes with a crucial process that allows cancer cells to reproduce and spread. Specifically, pemetrexed stops the production of three enzymes that are required to feed the cancer cell. Often used in combination with cisplatin. Marketed under the name ALIMTA. See: Alimta.

intraperitoneal chemotherapy

(IPC) a form of regional chemotherapy; the flooding of the abdominal cavity with chemotheraputic drugs to target the cancer cells directly. It is sometimes heated to improve absorption of the anticancer drugs by the cancerous cells and because heat itself can kill cancer cells.

Felip E, Rosell R.

Vall d’Hebron University Hospital Barcelona, Spain.

Abstract

NSCLC accounts for 80% of all cases of lung cancer, which is the leading cause of cancer mortality. The majority of NSCLC patients present with advanced, unresectable disease, which remains incurable. In advanced disease, chemotherapy with platinum (cisplatin or carboplatin) in combination with a third-generation cytotoxic drug (vinorelbine, gemcitabine, paclitaxel, or docetaxel) can provide a modest improvement in survival without impairing quality of life. In chemotherapy-naïve, advanced, non-squamous NSCLC patients, the combination of bevacizumab with chemotherapy was shown to produce better outcomes than chemotherapy alone. Response rates of 20%-40% can now be expected, with a median survival of 8-11 months and a 1-year survival rate of 30%-40%. In second-line treatment, docetaxel has shown superiority to best supportive care in terms of survival and quality of life. A pooled analysis comparing docetaxel administered weekly versus 3-weekly found similar survival rates between the schedules and a non-significant reduction in febrile neutropenia for the weekly regimen. Pemetrexed, a multitargeted antifolate agent, has shown clear activity in several tumors, including mesothelioma and NSCLC. In a phase III trial, second-line treatment with pemetrexed demonstrated overall survival comparable to docetaxel, with a more manageable toxicity profile.

Keywords: pemetrexed, second-line therapy, NSCLC

Glossary

therapy

any of the measures taken to treat a disease. Unproven therapy is any therapy that has not been scientifically tested and approved. Use of an unproven therapy instead of standard (proven) therapy is called alternative therapy. Some alternative therapies have dangerous or even life-threatening side effects. For others, the main danger is that a patient may lose the opportunity to benefit from standard therapy. Complementary therapy, on the other hand, refers to therapies used in addition to standard therapy. Some complementary therapies may help relieve certain symptoms of cancer, relieve side effects of standard cancer therapy, or improve a patient's sense of well-being. The ACS recommends that patients considering use of any alternative or complementary therapy discuss this with their health care team.

survival rate

the percentage of survivors with no trace of disease within a certain period of time after diagnosis or treatment. For cancer, a 5-year survival rate is often given. This does not mean that people can't live more than five years, or that those who live for 5 years are necessarily permanently cured.

regimen

(rej-uh-men) a strict, regulated plan (such as diet, exercise, or other activity) designed to reach certain goals. In cancer treatment, a plan to treat cancer.

mortality

a measure of the rate of death from a disease within a given population.

cytotoxic

(site-o-tox-ik) toxic to cells; cell-killing.

chemotherapy

(key-mo-THER-uh-pee) treatment with drugs to destroy cancer cells. Chemotherapy is often used with surgery or radiation to treat cancer when the cancer has spread, when it has come back (recurred), or when there is a strong chance that it could recur.

cancer

malignancy; a group of diseases typified by abnormal, generally out-of-control, cell growth.

mesothelioma

a tumor derived from mesothelial tissue, such as the peritoneum (lining the abdomen) or pleura (lining the lungs). More on mesothelioma.

pemetrexed

chemotheraputic agent that interferes with a crucial process that allows cancer cells to reproduce and spread. Specifically, pemetrexed stops the production of three enzymes that are required to feed the cancer cell. Often used in combination with cisplatin. Marketed under the name ALIMTA. See: Alimta.