Barone-Adesi F, Ferrante D, Bertolotti M, Todesco A, Mirabelli D, Terracini B, Magnani C.

Unit of Cancer Epidemiology, CeRMS and Center for Oncologic Prevention Piemonte, University of Turin, Turin, Italy.

Abstract

Models based on the multistage theory of carcinogenesis predict that the rate of mesothelioma increases monotonically as a function of time since first exposure (TSFE) to asbestos. Predictions of long-term mortality (TSFE >/= 40 years) are, however, still untested, because of the limited follow-up of most epidemiological studies. Some authors have suggested that the increase in mesothelioma rate with TSFE might be attenuated by clearance of asbestos from the lungs. We estimated mortality time trends from pleural and peritoneal cancer in a cohort of 3,443 asbestos-cement workers, followed for more than 50 years. The functional relation between mesothelioma rate and TSFE was evaluated with various regression models. The role of asbestos clearance was explored using the traditional mesothelioma multistage model, generalized to include a term representing elimination over time. We observed 139 deaths from pleural and 56 from peritoneal cancer during the period 1950-2003. The rate of pleural cancer increased during the first 40 years of TSFE and reached a plateau thereafter. In contrast, the rate of peritoneal cancer increased monotonically with TSFE. The model allowing for asbestos elimination fitted the data better than the traditional model for pleural (p = 0.02) but not for peritoneal cancer (p = 0.22). The risk for pleural cancer, rather than showing an indefinite increase, might reach a plateau when a sufficiently long time has elapsed since exposure. The different trends for pleural and peritoneal cancer might be related to clearance of the asbestos from the workers’ lungs.

Keywords: asbestos, mesothelioma, multi-stage model, latency, clearance

Glossary

mortality

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

epidemiology

(ep-uh-deem-ee-AHL-uh-gee) the study of diseases in populations by collecting and analyzing statistical data. In the field of cancer, epidemiologists look at how many people have cancer; who gets specific types of cancer; and what factors (such as environment, job hazards, family patterns, and personal habits, such as smoking and diet) play a part in the development of cancer.

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.

peritoneal

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

Ali Y, Lin Y, Gharibo MM, Gounder MK, Stein MN, Lagattuta TF, Egorin MJ, Rubin EH, Poplin EA.

The Cancer Institute of New Jersey, University of Medicine & Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, USA.

Abstract

Purpose: Preclinical data shows improvements in response for the combination of imatinib mesylate (IM, Gleevec) and gemcitabine (GEM) therapy compared with GEM alone. Our goals were to determine the maximum tolerated dose of GEM and IM in combination, the pharmacokinetics of GEM in the absence and in the presence of IM, and IM pharmacokinetics in this combination.

Patients and Methods: Patients with refractory malignancy, intact intestinal absorption, measurable/evaluable disease, adequate organ function, Eastern Cooperative Oncology Group PS 0-2, and signed informed consent were eligible. Initially, treatment consisted of 600 mg/m2 of GEM (10 mg/m2/min) on days 1, 8, and 15, and 300 mg of IM daily every 28 days. Due to excessive toxicity, the schedule was altered to IM on days 1 to 5 and 8 to 12, and GEM on days 3 and 10 every 21 days. Two final cohorts received IM on days 1 to 5, 8 to 12, and 15 to 19.

Results: Fifty-four patients were treated. IM and GEM given daily at 500 to 600 mg/m2 on days 1, 8, and 15 produced frequent dose-limiting toxicities. With the modified scheduling, GEM given at 1,500 mg/m2/150 min was deliverable, along with 400 mg of IM, without dose-limiting toxicities. Three partial (laryngeal, renal, and mesothelioma) and two minor (renal and pancreatic) responses were noted at GEM doses of 450 to 1,500 mg/m2. Stable disease >24 weeks was seen in 17 patients. CA19-9 in 7 of 10 patients with pancreatic cancer was reduced by 90%. IM did not significantly alter GEM pharmacokinetics.

Conclusion: The addition of intermittently dosed IM to GEM at low to full dose was associated with broad antitumor activity and little increase in toxicity.

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.

oncology

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

informed consent

a legal document that explains a course of treatment, the risks, benefits, and possible alternatives; the process by which patients agree to treatment.

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.

Alexandre Mathy^a, Paul Baas^b, Otilia Dalesio^a and Nico van Zandwijk^b

^aBiometrics Department, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
^bDepartment of Thoracic Oncology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands

Abstract

Twenty-five patients with histologically proven malignant mesothelioma participated in a trial of imatinib mesylate (Glivec) with a starting dose of 400 mg per day taken orally, up to a maximal dose of 800 mg. No responses were observed in the patient group, while three patients showed prolonged (> 6 months) stabilization of disease. The median survival time was 398 days (range 88–840); the median time to progression was 63 days (range 29–275). Side effects of the medication were mild and included edema, nausea, constipation and diarrhea. We conclude that further investigation with monotherapy imatinib in mesothelioma is not warranted.

Glossary

side effects

effects of treatment (other than the effects on the cancer) such as hair loss caused by chemotherapy, and fatigue caused by radiation therapy.

oncology

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

edema

(eh-deem-uh) build-up of fluid in the tissues, causing swelling. Edema of the arm can occur after radical mastectomy, axillary dissection of lymph nodes, or radiation therapy.

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.