nitrosourea compounds


Summary: A class of compounds in which the core molecule is R-NO, where R is UREA.

Top Publications

  1. Mornex F, Thomas L, Mohr P, Hauschild A, Delaunay M, Lesimple T, et al. [Randomised phase III trial of fotemustine versus fotemustine plus whole brain irradiation in cerebral metastases of melanoma]. Cancer Radiother. 2003;7:1-8 pubmed
    ..Fotemustine plus whole brain irradiation delayed the time to brain progression of melanoma cerebral metastases compared to fotemustine alone but without a significant improvement in terms of objective control or overall survival. ..
  2. Passagne I, Evrard A, Winum J, Depeille P, Cuq P, Montero J, et al. Cytotoxicity, DNA damage, and apoptosis induced by new fotemustine analogs on human melanoma cells in relation to O6-methylguanine DNA-methyltransferase expression. J Pharmacol Exp Ther. 2003;307:816-23 pubmed
    ..The ability of this compound to induce apoptosis in the absence of BG was confirmed by a specific enzyme-linked immunosorbent assay apoptotic assay using a single-stranded DNA monoclonal antibody. ..
  3. Scoccianti S, Detti B, Sardaro A, Iannalfi A, Meattini I, Leonulli B, et al. Second-line chemotherapy with fotemustine in temozolomide-pretreated patients with relapsing glioblastoma: a single institution experience. Anticancer Drugs. 2008;19:613-20 pubmed publisher
    ..Fotemustine has shown therapeutic efficacy as single-drug second-line chemotherapy in treatment of TMZ pretreated patients. ..
  4. Fazeny Dörner B, Veitl M, Wenzel C, Piribauer M, Rössler K, Dieckmann K, et al. Second-line chemotherapy with dacarbazine and fotemustine in nitrosourea-pretreated patients with recurrent glioblastoma multiforme. Anticancer Drugs. 2003;14:437-42 pubmed
    ..We conclude that the D/F combination is a well-tolerated second-line regimen and can be administered in a complete outpatient setting. D/F shows efficacy even in nitrosourea-pretreated patients and justifies further investigation. ..
  5. Dumontet C, Jaubert J, Sebban C, Bouafia F, Ardiet C, Tranchand B, et al. Clinical and pharmacokinetic phase II study of fotemustine in refractory and relapsing multiple myeloma patients. Ann Oncol. 2003;14:615-22 pubmed
    ..Fotemustine as a single agent has definite activity in patients with relapsing or refractory multiple myeloma, with acceptable toxicity and can be administered at conventional doses in patients with mild or moderate renal impairment. ..
  6. Jäckel A, Bock M, Deichmann M, Waldmann V, Naher H. [Therapy of metastatic malignant uveal melanoma]. Hautarzt. 2001;52:98-103 pubmed
    ..Following the characterisation of primary uveal melanoma, we summarize the results of different treatment protocols for metastatic disease and give an overview of new strategies. ..
  7. Petrovic I, Koricanac L, Todorovic D, Ristic Fira A, Valastro L, Privitera G, et al. Viability of a human melanoma cell after single and combined treatment with fotemustine, dacarbazine, and proton irradiation. Ann N Y Acad Sci. 2007;1095:154-64 pubmed
    ..Since the time point for measuring cumulative effects of drug and irradiation was 48 h post irradiation, it seems that the obtained level of viability could be attributed primarily to the effects of drugs. ..
  8. Silvani A, Lamperti E, Gaviani P, Eoli M, Fiumani A, Salmaggi A, et al. Salvage chemotherapy with procarbazine and fotemustine combination in the treatment of temozolomide treated recurrent glioblastoma patients. J Neurooncol. 2008;87:143-51 pubmed
    ..7-24.8). We concluded that the PCB + FTM combination as done in the current trial for patients with recurrent GBM after treatment with TMZ showed some benefit with regards to increased survival and that a Phase III trial is warranted...
  9. Brandes A, Tosoni A, Franceschi E, Blatt V, Santoro A, Faedi M, et al. Fotemustine as second-line treatment for recurrent or progressive glioblastoma after concomitant and/or adjuvant temozolomide: a phase II trial of Gruppo Italiano Cooperativo di Neuro-Oncologia (GICNO). Cancer Chemother Pharmacol. 2009;64:769-75 pubmed publisher
    ..Moreover, this is the first study to evaluate correlation between MGMT promoter status and outcome of fotemustine for relapsing GBM previously treated with radiotherapy and temozolomide. ..

More Information


  1. Paccapelo A, Lolli I, Fabrini M, Silvano G, Detti B, Perrone F, et al. A retrospective pooled analysis of response patterns and risk factors in recurrent malignant glioma patients receiving a nitrosourea-based chemotherapy. J Transl Med. 2012;10:90 pubmed publisher
    ..Time after the completion of radiotherapy and second surgery are independent treatment-related risk factors that were predictive of clinical benefit. ..
  2. Demidem A, Morvan D, Papon J, de Latour M, Madelmont J. Cystemustine induces redifferentiation of primary tumors and confers protection against secondary tumor growth in a melanoma murine model. Cancer Res. 2001;61:2294-300 pubmed
  3. Fabi A, Metro G, Russillo M, Vidiri A, Carapella C, Maschio M, et al. Treatment of recurrent malignant gliomas with fotemustine monotherapy: impact of dose and correlation with MGMT promoter methylation. BMC Cancer. 2009;9:101 pubmed publisher
    ..By determination of the MGMT promoter methylation status patients might be identified who are more likely to benefit from fotemustine chemotherapy. ..
  4. Mornex F, Thomas L, Mohr P, Hauschild A, Delaunay M, Lesimple T, et al. A prospective randomized multicentre phase III trial of fotemustine plus whole brain irradiation versus fotemustine alone in cerebral metastases of malignant melanoma. Melanoma Res. 2003;13:97-103 pubmed
  5. Avril M, Aamdal S, Grob J, Hauschild A, Mohr P, Bonerandi J, et al. Fotemustine compared with dacarbazine in patients with disseminated malignant melanoma: a phase III study. J Clin Oncol. 2004;22:1118-25 pubmed
    ..ORR was higher in the fotemustine arm compared to the DTIC arm in first-line treatment of disseminated melanoma. A trend in favor of fotemustine in terms of overall survival and time to BM was evidenced. ..
  6. Daponte A, Ascierto P, Gravina A, Melucci M, Palmieri G, Comella P, et al. Cisplatin, dacarbazine, and fotemustine plus interferon alpha in patients with advanced malignant melanoma. A multicenter phase II study of the Italian Cooperative Oncology Group. Cancer. 2000;89:2630-6 pubmed
    ..However, considering the currently available therapies, this regimen does not seem to offer a special advantage in the treatment of patients with this disease. New agents and new protocols are needed. ..
  7. Weichenthal M, Mohr P, Stephan U, Altenhoff J, Kowalzick L, Marseille A, et al. Fotemustine and interferon alpha2b in metastatic malignant melanoma. J Cancer Res Clin Oncol. 1998;124:55-9 pubmed
    ..The combination of fotemustine with IFNalpha is effective and well tolerated, but there is no evident advantage over fotemustine monotherapy in the treatment of metastatic melanoma. ..
  8. De Rossi A, Rossi L, Laudisi A, Sini V, Toppo L, Marchesi F, et al. Focus on Fotemustine. J Exp Clin Cancer Res. 2006;25:461-8 pubmed
    ..Therefore, it is reasonable to assume that this agent could be a good candidate to play a potential role in haematological malignancies. ..
  9. Musso M, Scalone R, Marcacci G, Lanza F, Di Renzo N, Cascavilla N, et al. Fotemustine plus etoposide, cytarabine and melphalan (FEAM) as a new conditioning regimen for lymphoma patients undergoing auto-SCT: a multicenter feasibility study. Bone Marrow Transplant. 2010;45:1147-53 pubmed publisher
    ..4%. We conclude that a FEAM regimen is feasible and safe. Although toxicity and engraftment times compared favorably with BEAM, longer follow-up is needed to evaluate fully its efficacy and long-term safety. ..
  10. Ozkan M, Altinbas M, Er O, Kaplan B, Coskun H, Karahacioglu E, et al. Post-operative sequential chemo-radiotherapy in high-grade cerebral gliomas with fotemustine. J Chemother. 2004;16:298-302 pubmed
    ..This trial demonstrates that postoperative radiotherapy and sequential fotemustine therapy is feasible, well tolerated, and may prolong survival in patients with newly diagnosed high-grade gliomas. ..
  11. Bajetta E, Del Vecchio M, Bernard Marty C, Vitali M, Buzzoni R, Rixe O, et al. Metastatic melanoma: chemotherapy. Semin Oncol. 2002;29:427-45 pubmed
    ..New chemotherapeutic and biologic agents are now available and promising combined approaches targeting the tumor by several different mechanisms are desirable and will probably represent the future modality of treatment. ..
  12. Di Giacomo A, Ascierto P, Pilla L, Santinami M, Ferrucci P, Giannarelli D, et al. Ipilimumab and fotemustine in patients with advanced melanoma (NIBIT-M1): an open-label, single-arm phase 2 trial. Lancet Oncol. 2012;13:879-86 pubmed publisher
    ..The combination of ipilimumab plus fotemustine has clinical activity in patients with metastatic melanoma, including those with brain metastases. Bristol-Myers Squibb. ..
  13. Silvani A, Gaviani P, Lamperti E, Botturi A, Ferrari D, Simonetti G, et al. Lecture: fotemustine in brain tumors. Neurol Sci. 2011;32 Suppl 2:S255-7 pubmed publisher
    ..Recently, some authors reported the interesting results of a multicenter study on recurrent glioblastoma multiforme patients combining FTMS with new antiangiogentic agent bevacizumab. ..
  14. Leyvraz S, Spataro V, Bauer J, Pampallona S, Salmon R, Dorval T, et al. Treatment of ocular melanoma metastatic to the liver by hepatic arterial chemotherapy. J Clin Oncol. 1997;15:2589-95 pubmed
    ..It involves no major toxicity and preserves the quality of life. To assess further its effectiveness, a randomized study to compare hepatic intraarterial versus intravenous chemotherapy is being planned. ..
  15. Cellarier E, Terret C, Labarre P, Ouabdesselam R, Cure H, Marchenay C, et al. Pharmacokinetic study of cystemustine, administered on a weekly schedule in cancer patients. Ann Oncol. 2002;13:760-9 pubmed
    ..001). A reasonable starting dose for phase II studies is 40 mg/m2, with dose escalation based on blood cell counts. ..
  16. Del Vecchio M, Mortarini R, Canova S, Di Guardo L, Pimpinelli N, Sertoli M, et al. Bevacizumab plus fotemustine as first-line treatment in metastatic melanoma patients: clinical activity and modulation of angiogenesis and lymphangiogenesis factors. Clin Cancer Res. 2010;16:5862-72 pubmed publisher
    ..The combination of bevacizumab plus fotemustine has clinical activity in advanced melanoma and promotes systemic modulation of angiogenesis and lymphangiogenesis factors. ..
  17. Addeo R, Caraglia M, De Santi M, Montella L, Abbruzzese A, Parlato C, et al. A new schedule of fotemustine in temozolomide-pretreated patients with relapsing glioblastoma. J Neurooncol. 2011;102:417-24 pubmed publisher
    ..The study demonstrates that FTM has therapeutic efficacy as single-drug second-line chemotherapy with a favorable safety profile. ..
  18. Kaina B, Mühlhausen U, Piee Staffa A, Christmann M, Garcia Boy R, Rösch F, et al. Inhibition of O6-methylguanine-DNA methyltransferase by glucose-conjugated inhibitors: comparison with nonconjugated inhibitors and effect on fotemustine and temozolomide-induced cell death. J Pharmacol Exp Ther. 2004;311:585-93 pubmed
    ..Therefore, O(6)BTG-C8-betaGlu seems to be especially suitable for approaching MGMT inhibitor targeting in tumor therapy. ..
  19. Fabrini M, Silvano G, Lolli I, Perrone F, Marsella A, Scotti V, et al. A multi-institutional phase II study on second-line Fotemustine chemotherapy in recurrent glioblastoma. J Neurooncol. 2009;92:79-86 pubmed publisher
    ..1 months; PFS-6 was 52% and median overall survival from primary diagnosis was 24.5 months, with few manageable haematological toxicities. Fotemustine was safe and effective as second-line chemotherapy in recurrent glioblastoma. ..
  20. Frytak S, Moertel C, O Fallon J, Rubin J, Creagan E, O Connell M, et al. Delta-9-tetrahydrocannabinol as an antiemetic for patients receiving cancer chemotherapy. A comparison with prochlorperazine and a placebo. Ann Intern Med. 1979;91:825-30 pubmed
    ..Although THC may have a role in preventing nausea and vomiting associated with cancer chemotherapy, this role must be more clearly defined before THC can be recommended for general use. ..
  21. Durando X, Thivat E, D Incan M, Sinsard A, Madelmont J, Chollet P. Long-term disease-free survival in advanced melanomas treated with nitrosoureas: mechanisms and new perspectives. BMC Cancer. 2005;5:147 pubmed
    ..But despite these noteworthy and encouraging but also rare results, it appears essential to increase Cystemustine efficiency. ..
  22. Lee S, Margison G, Thatcher N, O Connor P, Cooper D. Formation and loss of O6-methyldeoxyguanosine in human leucocyte DNA following sequential DTIC and fotemustine chemotherapy. Br J Cancer. 1994;69:853-7 pubmed
  23. Bourg V, Lebrun C, Chichmanian R, Thomas P, Frenay M. Nitroso-urea-cisplatin-based chemotherapy associated with valproate: increase of haematologic toxicity. Ann Oncol. 2001;12:217-9 pubmed
    ..Haematologic side-effects decrease after AED modification during the continued chemotherapy. This adverse event should be managed with caution. ..
  24. Handa H, Irisawa H, Komatsumoto S, Matsushima T, Tsukamoto N, Nojima Y, et al. [Plasmacytoma with multiple hypervascular lesions revealed by angiography in a patient with multiple myeloma]. Rinsho Ketsueki. 2006;47:521-5 pubmed
    ..She was discharged and treated as an outpatient but relapsed and died of chemotherapy-resistant myeloma. We report this case because macro-angiogenesis in a multiple myeloma demonstrated by angiography is rare and interesting. ..
  25. Yamada Y, Tomonaga M, Fukuda H, Hanada S, Utsunomiya A, Tara M, et al. A new G-CSF-supported combination chemotherapy, LSG15, for adult T-cell leukaemia-lymphoma: Japan Clinical Oncology Group Study 9303. Br J Haematol. 2001;113:375-82 pubmed
    ..LSG15 is feasible with mild non-haematological toxicity and improved the clinical outcome of ATL patients. MST and overall survival at 2 years were superior to those obtained by our previous trials. ..
  26. Suzui M, Sugie S, Mori H, Okuno M, Tanaka T, Moriwaki H. Different mutation status of the beta-catenin gene in carcinogen-induced colon, brain, and oral tumors in rats. Mol Carcinog. 2001;32:206-12 pubmed
    ..Thus, the mutation spectrum in the beta-catenin gene is organ- and chemical carcinogen-specific...
  27. De Felice F, Bulzonetti N, Musio D, D Elia A, Salvati M, Tombolini V. Low-dose fotemustine as second-line chemotherapy for recurrent glioblastoma multiforme. Anticancer Res. 2013;33:4013-6 pubmed
    ..This low-dose approach could be considered a compromise treatment whilst waiting for definitive standardization of second-line therapy, in order to reduce severe hematological toxicity. ..
  28. Fazeny Dörner B, Veitl M, Wenzel C, Rossler K, Ungersböck K, Dieckmann K, et al. Survival with dacarbazine and fotemustine in newly diagnosed glioblastoma multiforme. Br J Cancer. 2003;88:496-501 pubmed
    ..No other toxicities of NCI-CTC grade 3 or 4 occurred. The treatment is feasible in a complete outpatient setting and the results of the D/F regimen justify further investigations with these compounds. ..
  29. Gorbunova V, Orel N, Semina O, Besova N, Kadagidze Z. [Nitrullin -- a new original Russian drug of the nitrosomethylurea group]. Vopr Onkol. 2001;47:680-3 pubmed
    ..Nutrullin had immuno-modulating effect. Its application alone or in combination with VPN showed good results in the management of small-cell cancer of the lung. ..
  30. Morales Ramirez P, Cruz Vallejo V, Rodríguez Reyes R. Differences in sensitivity of murine spermatogonia and somatic cells in vivo to sister-chromatid exchange induction by nitrosoureas. Mutat Res. 2001;478:185-90 pubmed
    ..This implies that SPG are also less sensitive to SCE induction by nitrosoureas, which cause a different kind of damage from previously assayed mutagens. ..
  31. Holen K. Therapeutic and palliative options for diffuse neuroendocrine metastatic disease. J Gastrointest Surg. 2006;10:337-40 pubmed
  32. Samanta S, Pain A, Dutta S, Sanyal U. Synthesis and evaluation of 2-chloroethylnitrosoureas of substituted naphthalimides as mixed-function anticancer compounds. Acta Pol Pharm. 2001;58:351-6 pubmed
    ..These were further screened in vitro in 6 different human tumour cell lines but no significant activity was observed in those lines. ..
  33. Hirose Y, Masaki Y, Sugai S. Leukemic transformation with trisomy 8 in essential thrombocythemia: a report of four cases. Eur J Haematol. 2002;68:112-6 pubmed
    ..It is suggested that progression of the disease may have increased the incidence of trisomy 8 and the development of leukemic transformation. ..
  34. Monneret C, Risse S, Ardouin P, Gouyette A. Synthesis and antitumour activity of a new series of nitrosoureido sugars. Eur J Med Chem. 2000;35:137-46 pubmed
    ..Owing to its lower acute toxicity, methyl 3-[3-(2-chloroethyl)-3-nitrosoureido]-3, 4-dideoxy-beta-D-arabino-hexopyranoside 24 appeared as the best candidate for preclinical studies...
  35. Addeo R, Zappavigna S, Luce A, Facchini S, Caraglia M. Chemotherapy in the management of brain metastases: the emerging role of fotemustine for patients with melanoma and NSCLC. Expert Opin Drug Saf. 2013;12:729-40 pubmed publisher
    ..FTM is a third-generation nitrosourea that has proved its efficacy on brain metastases of melanoma and showed promising results for the treatment of brain metastasis of NSCLC because of its ability to pass the blood-brain barrier. ..
  36. Pain A, Samanta S, Dutta S, Saxena A, Shanmugavel M, Sharma M, et al. Synthesis and evaluation of ethylnitrosoureas of substituted naphthalimides as anticancer compounds. Acta Pol Pharm. 2007;64:27-33 pubmed
    ..Three compounds were further screened in vitro in 4 different human tumor cell lines but no significant activity was observed in those lines. These compounds moderately inhibit the synthesis of DNA and RNA in S-180 tumor cells. ..
  37. Murakami H, Yamane A, Sawamura M, Matsumoto M, Murayaman K, Shimano S, et al. Combination chemotherapy of ranimustine, doxorubicine, and dexamethasone for relapsing multiple myeloma--a pilot study. J Med. 2003;34:39-46 pubmed
    ..3%. Toxicity and adverse events during RAD therapy were tolerable. This pilot study demonstrated that RAD therapy is useful for the treatment o frefractory myeloma. ..
  38. Carpentier A. Neuro-oncology: the growing role of chemotherapy in glioma. Lancet Neurol. 2005;4:4-5 pubmed
  39. Won J, Marin de Evsikova C, Smith R, Hicks W, Edwards M, Longo Guess C, et al. NPHP4 is necessary for normal photoreceptor ribbon synapse maintenance and outer segment formation, and for sperm development. Hum Mol Genet. 2011;20:482-96 pubmed publisher
    ..Although Nphp4(nmf192/nmf192) mice fail to recapitulate the kidney phenotype of NPHP, they will provide a valuable tool to further elucidate how NPHP4 functions in the retina and male reproductive organs. ..
  40. Santoni M, Paccapelo A, Burattini L, Onofri A, Cascinu S. Twice-daily dosing of temozolomide in combination with fotemustine for the treatment of patients with refractory glioblastoma. Anticancer Res. 2012;32:1099-101 pubmed
    ..Results indicate that our temozolomide -FTM combined schedule is not effective, although well tolerated, in non responsive patients with GBM. Further strategies are required to improve the outcome of these patients. ..
  41. Avril M. [Fotemustine: muphoran]. Ann Dermatol Venereol. 2007;134:997-1000 pubmed
  42. Passagne I, Evrard A, Depeille P, Cuq P, Cupissol D, Vian L. O(6)-methylguanine DNA-methyltransferase (MGMT) overexpression in melanoma cells induces resistance to nitrosoureas and temozolomide but sensitizes to mitomycin C. Toxicol Appl Pharmacol. 2006;211:97-105 pubmed
    ..This observation suggests that glutathione is involved in the sensitivity of MGMT-transfected cells to mitomycin C and may act synergistically with MGMT via an unknown mechanism. ..
  43. Wittig R, Nessling M, Will R, Mollenhauer J, Salowsky R, Münstermann E, et al. Candidate genes for cross-resistance against DNA-damaging drugs. Cancer Res. 2002;62:6698-705 pubmed
    ..As MPP1 and CRYAB are also among the 14 genes differentially expressed in all three of the drug-resistant sublines, they represent the strongest candidates for resistance against DNA-damaging drugs. ..
  44. Kiss A, Remenyi G, Szasz R, Batar P, Rejto L, Váróczy L, et al. [One hundred fifty autologous peripheral haemopoietic stem cell transplantations and their lessons]. Orv Hetil. 2009;150:1251-7 pubmed publisher
    ..This centre performed the largest quantity of the conditioning protocol Zevalin, Bischloronitrosourea, Etoposide, cytosine-Arabinoside, Melphalan in non-Hodgkin lymphoma in Hungary; ten patients were treated with this protocol. ..
  45. Karpenko L. [Experience with use of mustoforan at the Clinical Oncological Dispensary of the Republic of Tatarstan]. Vopr Onkol. 2005;51:388-90 pubmed
  46. Fukushima T, Katayama Y, Watanabe T, Yoshino A, Ogino A, Ohta T, et al. Promoter hypermethylation of mismatch repair gene hMLH1 predicts the clinical response of malignant astrocytomas to nitrosourea. Clin Cancer Res. 2005;11:1539-44 pubmed
    ..The findings obtained suggest that determination of the methylation status of hMLH1 could provide a potential basis for designing rational chemotherapeutic strategies, as well as for predicting prognosis. ..
  47. Carrillo J, Munoz C. Alternative chemotherapeutic agents: nitrosoureas, cisplatin, irinotecan. Neurosurg Clin N Am. 2012;23:297-306, ix pubmed publisher
    ..The activity of these chemotherapeutic agents in brain tumors will likely ensure a place in the armamentarium of neuro-oncologists for many years. ..
  48. Uzuka T, Tanaka R, Takahashi H, Kakinuma K, Matsuda J, Kato K. Planning of hyperthermic treatment for malignant glioma using computer simulation. Int J Hyperthermia. 2001;17:114-22 pubmed
    ..0%). These results demonstrate that this novel treatment planning method may prove to be a clinically valuable tool in the treatment of malignant glioma with RF electrodes. ..
  49. Ferrezuelo F, Prieto Alamo M, Jurado J, Pueyo C. Role of DNA repair by (A)BC excinuclease and Ogt alkyltransferase in the final distribution of LacI-d mutations induced by N-butyl-N-nitrosourea in Escherichia coli. Mutagenesis. 1998;13:507-14 pubmed
  50. Peters S, Voelter V, Zografos L, Pampallona S, Popescu R, Gillet M, et al. Intra-arterial hepatic fotemustine for the treatment of liver metastases from uveal melanoma: experience in 101 patients. Ann Oncol. 2006;17:578-83 pubmed
    ..Median survival rates are among the longest reported and one-third of the patients are still alive at 2 years. ..
  51. Shibui S. [Resent advances in chemotherapy for malignant brain tumors]. Gan To Kagaku Ryoho. 2005;32:442-7 pubmed
    ..It can be a model of clinical trials for malignant brain tumors in Japan. ..
  52. Ivanov I, Gadjeva V. Influence of some DNA-alkylating drugs on thermal stability, acid and osmotic resistance of the membrane of whole human erythrocytes and their ghosts. Pharmazie. 2000;55:672-7 pubmed
    ..The present study gives direct evidence that alkylating agents, having a high therapeutic activity against malignant growth, bind covalently to proteins of cellular membranes. ..
  53. Briscoe W, Anderson S, May H. Base sequence specificity of three 2-chloroethylnitrosoureas. Biochem Pharmacol. 1990;40:1201-9 pubmed