Language: Spanish
References: 28
Page: 62-67
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ABSTRACT
Background: In Mexico during 1997, more than 87,000 new cancer patients were registered. The most frequent tumours were cervix, breast, prostate, lymph nodes, and stomach. Angiogenesis is an important factor for tumour growth and proliferation as well as for conferring metastatic potential. Thalidomide was vinculated with teratogenesis in the 1950s; it is capable to inhibit angiogenesis, induce apoptosis, and has inmunomodulatory effects.
Objective: To evaluate the tolerability and safety of thalidomide as an antiangiogenic agent in patients with advanced tumours.
Patients and methods: Patients of age 18 years of both genders, with metastatic cancer heavily pre-treated, refractary, or with progression to conventional therapy. Patients received thalidomide as monotherapy, for at least 1 month. Thalidomide at the starting dose of 100 mg/day p.o. in an escalation fashions of 200 mg the first week and then every 15 days up to 800 mg. We registered age, gender, type of neoplasm, histology, clinical stage, thalidomide doses, length of therapy, side effects and follow-up time.
Results: Thirteen patients, three females, 10 males, mean age 57.8 ± 14.6 years, range 31 to 76 years. Tumours included: in 10 solid neoplasms and three hematologic in that were three hepatocarcinoma, two multiple myeloma, two malignant melanoma, two lung, and breast, colon, rectum and non-Hodgkin lymphoma, one case each. Of 10 solid neoplasms, there were, seven in EC IV (70%) and three EC III (30%); of the hematologic neoplasms, two were Durie-Salomon II, and lymphoma in stage IV. Eight patients had metastatic activity, 61.5%. Five patients had received one chemotherapy scheme previously, six, two schemes, and two patients, three schemes. Thalidomide doses: four patients received 100 mg/day, seven, 200 mg; one, 300 mg, and one, 400 mg/day; only in two patients did we attempt to escalate doses. Mean time use of thalidomide 3.15 ± 3.78 months, range one to 12. Ten patients had side effects, 76.9%; sleepiness, eight patients, 61.5%; six, peripheric sensorial neuropathy, 46.1% and one rash, 7.7%. Four cases of stable disease and eight with progression were observed.
Conclusions: Thalidomide was adequately tolerated at doses of 100 to 200 mg/day; it is associated with sleepiness and weakness of low grade, and side effects increased when the dose was escalated. Further studies should be designed to evaluate antitumour effect, proper dosage and association with chemotherapy, biologic, or immunomodulatory agents.
REFERENCES
Registro Histopatológico de Neoplasias en México. Dirección General de Epidemiología, Secretaría de Salud. 1997: 9-13.
Folkman J. What is the evidence that tumours are angiogenesis dependent? J Natl Cancer Inst 1990; 82: 4-6.
Weidner L. The relationship of tumour angiogenesis and metastasis with emphasis on invasive breast carcinoma. Adv Pathol Lab Med. 1992; 5: 101-21.
Weidner N. Tumour angiogenesis: review of current applications in tumour prognostication. Sem Diag Pathol 1993; 10: 302-13.
Folkman J. Angiogenesis and breast cancer. J Clin Oncol 1994; 12(3): 441-43.
Pudla JM. Tumour associated angiogenesis: mechanisms, clinical implications, and the therapeutic strategies. Semin Oncol 1997; 24(2): 203-18.
Folkman J, Watson K, Ingber D, et al. Induction of angiogenesis during the transition from hiperplasia to neoplasia. Nature 1989; 339: 58-61.
Klagsbrun M, Amore PA. Regulators of angiogenesis. Ann Rev Physiol 1991; 53: 217-39.
Watson JC, Redmann JG, Meyers MO, et al. Breast cancer increases initiation of angiogenesis without accelerating neovesseis growth rate. Surgery 1997; 122: 508-13.
Horak E, Leek R, Klenk N, et al. Angiogenesis assessed by platelet/endothelial cell adhesion molecule antibodies, as indicator of node metastases and survival in breast cancer. Lancet 1992; 340: 1120-24.
Heimann R, Ferguson D, Powers C, et al. Angiogenesis as a predictor of long-term survival for patients wit node-negative breast cancer. J Natl Cancer Inst 1996; 88: 1764-9.
Quilitz R. Thalidomide in oncology; the peril and the promise. JMCC 1999; 6: 483-95.
D’Amato RJ, Loughnan MS, Flynn E, et al. Thalidomide is an inhibitor of angiogenesis. Proc Natl Acad Sci USA 1994; 91: 4082-5.
Singhal S, Mehta J, Desikan R, et al. Antitumour activity of thalidomide in refractory multiple myeloma. N Engl Med 1999; 341: 1565-71.
Kotoh T, Dhar DK, Masunaga R et al. Antiangiogenic therapy of human oesophageal cancers with thalidomide in nude mice. Surgery 1999; 125: 536-44.
Fine HA, Figg WD, Jaeck1e K et al. Phase II trial of the antiangiogenic agent thalidomide in patients with recurrent high-grade gliomas. J Clin Oncol 2000; 18: 708-15.
Munshi N, Desikan R, Zangari M et al. Chemoangiotherapy with DT-pace for previously treated multiple myeloma (MM). Am Soc Hematol 1999; Abst 540.
Moehler TM, Naben K, Egerer G, et al. Thalidomide plus CED-chemotherapy in patients with poor prognosis multiple myeloma. Am Soc Hematol, 1999; Abst 547.
Sabir T, Raza S, Anderson L et al. Thalidomide is effective in the treatment of recurrent refractory multiple myeloma (MM). Am Soc Hematol 1999; Abst 548.
Rajkumar SV, Fonseca R, Dispenzieri A et al. Thalidomide in the treatment of relapsed and refractory myeloma. Am Soc Hematol 1999; Abst 1414.
Schiller G, Vescio R, Berenson J. Thalidomide for the treatment of multiple myeloma relapsing after autologous peripheral blood progenitor cell transplant. Am Soc Hematol 1999; Abst 1417.
Weber DM, Gavino M, Delasalle K et al. Thalidomide alone or with dexamethasone for multiple myeloma. Am Soc Hematol 1999; Abst 2686.
Chen CI, Adesanya A, Sutton DM et al. Low-dose thalidomide in patients with advanced refractory multiple myeloma. Am Soc Hematol 1999; Abst 4603.
Perry MC. World Health Organization toxicity guidelines. In: Perry MC. The chemotherapy source book. Baltimore, MO, USA: Williams and Wilkins editors. 1992: 1132-1144.
Thomas DA, Aguayo A, Estey E et al. Thalidomide as anti-angiogenesis therapy (Rx) in refractory or relapsed leukaemia. Am Soc Hematol 1999; Abst 2269.
Raza S, Lisak L, Andrews C et al. Thalidomide produces transfusion independence in patients with long standing refractory anaemias and myelodisplastic syndromes (MDS). Am Soc Hematol 1999; Abst 2935.
Thomas DA, Aguayo A, Giles FJ et al. Thalidomide anti-angiogenesis therapy (RX) in Philadelphia (Ph) negative myeloproliferative disorders (MPD) and myelofibrosis (MF). Am Soc Hematol 1999; Abst 3102.
Raje N, Anderson K, Thalidomide-a revival story. N Engl J Med 1999; 341: 1606-8.
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