Summary
In a phase II cooperative study involving eleven Italian haematological units, the efficacy and toxicity of a new alkylating compound, PTT-119, was evaluated in 53 patients with non-Hodgkin's lymphoma (NHL). Forty-five of the patients had been previously treated with various regimens of chemotherapy, the remaining eight were at the onset of the disease. PTT-119 was scheduled at 3.0 mg/kg every three weeks for a minimum of three administrations. Seven patients achieved a complete remission (CR), 19 a partial remission (PR); the overall response rate was 49%. The median duration of response was 6 months. Most frequent adverse effects were alopecia, nausea and vomiting and phlebitis due to the drug infusion. Myelosuppression was severe only in patients with bone marrow involvement or who were heavily pretreated. No liver, cardiac or renal toxicity was recorded. These data indicate that PTT-119 is an effective drug in the treatment of NHL; the matter of its non-crossresistance with other alkylating compounds warrants further studies.
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Adelstein DJ, Lazarus HM, Hines JD, Herzig RH (1985) High-dose cytosine arabinoside in previously treated patients with poor-prognosis non-Hodgkin's lymphoma. Cancer 56: 1493–1496
Bajetta E, Buzzoni R, Viviani S (1985) Phase II study with amsacrines (m-AMSA and m-AMSA-lactate) in refractory lymphomas. Cancer Treat Rep 69: 965–969
Bianchi R, Nardelli B, Allegrucci M, Fioretti MC (1985) Efficacia terapeutica del PTT-119 valutata in vivo in modelli sperimentali. G Ital Chemioter 32: 1–16
Coppi G, Berti MA, Gatti T, Mosconi P (1984) Some pharmacological studies on a new tripeptide mustard. Il Farmaco Ed Sci 39: 26
Coppi G, Mosconi P, Gatti MT, Berti MA (1984) Chemotherapeutical, pharmacological and toxicological properties of PTT-119, a new antitumor agent. 1st European Conference on Advances in Antitumor Agents, Milano, May 30–June 1
De Barbieri A, Dall'Asta L, Comini A, Springolo V, Mosconi P, Coppi G, Bekesi G (1983) Synthesis, acute toxicity and chemotherapeutic anti-cancer activity of a new tripeptidic mustard. II Farmaco 38: 205–218
DeVita VT jr, Canellos GP, Chabner BA, Schein P, Hubbard SP, Young RC (1975) Advanced diffuse histiocytic lymphoma, a potentially curable disease: results with combination chemotherapy. Lancet I: 248–250
Elias L, Portlock CS, Rosenberg SA (1978) Combination chemotherapy of diffuse histiocytic lymphoma with cyclophosphamide, adriamycin, vincristine and prednisone (CHOP). Cancer 42: 1705–1710
Fisher RI, DeVita VT jr, Hubbard SM (1983) Diffuse aggressive lymphomas: increased survival after flexible sequences of Pro-MACE and MOPP chemotherapy. Ann Int Med 96: 304–309
Fisher RI, DeVita VT jr, Hubbard SM (1984) Randomized trial of ProMACE-MOPP vs. ProMACE-CytaBOM in previously untreated, advanced stage diffuse aggressive lymphomas. Proc Am Soc Clin Oncol 3: C-945
Guglielmi C, Amadori S, Anselmo AP, Baroni CD, Biagini C, Cimino G, Papa G, Mandelli F (1987) Sequential chemotherapy of high-grade non-Hodgkin's lymphoma with 5-fluorouracil, methotrexate, cytosine-arabinoside, cyclophosphamide, doxorubucin, vincristine and prednisone (F-MACHOP). Cancer Invest 5: 159–169
Klimo P, Connors JM (1985) MACOP-B Chemotherapy for the treatment of diffuse large-cell lymphoma. Ann Int Med 102: 596–602
Laurence J, Coltman M, Allen SL, Silver RT, Pasmantier M (1982) Combination chemotherapy of advanced diffuse histiocytic lymphoma with the six drug COP-BLAM regimen. Ann Int Med 97: 190–195
Lemoli RM, Visani G, Tosi P, Mazza P, Motta MR, Rizzi S, Zinzani PL, Poluzzi C, Gherlinzoni F, Tura S (1988) Effects of a new bifunctional alkylating agent (PTT-119) on in vitro growth of human cell lines and normal myeloid progenitors (CFU-GM). Haematologica 73: 195–200
Lennert K, Mhori M, Stein H (1975) The histopathology of malignant lymphomas. Br J Haematol [Suppl] 31: 193–203
Martoni A, Mazzei T, Mini E (1986) Phase I trial of a novel alkylating agent, PTT-119. Cancer Chemother Pharmacol 18: 192 (abstr)
Mini E, Mazzei T, Coronnello M, Criscuoli L, Gualtieri M, Periti P (1986) Efficacy of 3-(p-fluorophenyl)-L-alanyl-3-mbis (2-chloroethyl) amino-phenyl-L-methionine-ethoxy HCL (PTT-119) on human leukemic cell lines. 19th Int Cancer Congr, Budapest, August 21–27
Periti P, Mazzei T, Mini E (1986) Phase I clinical trial of a new alkylating agent, PTT-119. 19th Int Cancer Congress, Budapest, August 21–27
Rodriguez V, Cabanillas F, Burgess MA (1977) Combination chemotherapy (CHOP-Bleo) in advanced non-Hodgkin's malignant lymphomas. Blood 49: 325–339
Schein PS, DeVita VT jr, Hubbard S (1976) Bleomycin, adriamycin, cyclophosphamide, vincristine and prednisone (BACOP) combination chemotherapy in the treatment of advanced diffuse histiocytic lymphoma. Ann Int Med 85: 417–422
Schipp M, Klatt M, Harrington D (1985) M-BACOD and m-BACOD in the treatment of unfavourable prognosis lymphoma: analysis of prognostic variables. Proc Am Soc Oncol 4: C-799
Skarin AT, Canellos GP, Rosenthal DS (1983) Improved prognosis of diffuse histiocytic and undifferentiated lymphoma by use of high dose methotrexate alternating with standard agents (M-BACOD). J Clin Oncol 1: 91–98
Sweet C, Golomb HM (1980) The treatment of histiocytic lymphoma. Semin Oncol 7: 302–309
The Non Hodgkin's Lymphoma Pathologic Classification Project (1982) National Cancer Institute sponsored study of classification of non-Hodgkin's lymphomas. Summary and description of a Working Formulation for clinical usage. Cancer 49: 2112–2135
Tura S, Mazza P, Gherlinzoni F, Zinzani PL, Poletti G, Visani G, Lemoli RM, Cavo M, Galieni P, Tassi C, Zanchini R (1989) Phase II study of a new alkylating agent (PTT-119) in resistant-relapsed non Hodgkin's lymphomas. Cancer Chem Pharmacol 23: 123–125
WHO: WHO Handbook for reporting results of cancer treatment (1979) WHO Offset Publication 48, WHO, Geneve
Yagi MJ, Bekesi JG, Daniel MD, Holland JF, De Barbieri A (1984) Increased canceridal activity of PTT-119, a new synthetic bis-(2-chlorethyl) amino-L-phenylalanine derivative with carrier amino acids. In vitro bioassays. Cancer Chemother Pharmacol 12: 70–76
Yagi MJ, Chin SE, Holland JF, Bekesi JG (1985) Effectiveness of PTT-119 against susceptible and drug-resistant tumor cells. Proc Am Soc Cancer Res 26: 336
Yagi MJ, Chin SE, Scanlon KJ, Holland JF, Bekesi JG (1985) PTT-119, p-F-M-bis-(2-chloroethyl) amino-L-Phe-Met-Ethoxy HCL, a new chemotherapeutic agent active against drug-resistant tumor cell lines. Biochem Pharmacol 34: 2347–2354
Yagi MJ, Zanjani M, Holland JF, Bekesi JG (1984) Increased canceridal activity of PTT-119, a new synthetic bis-(2-chloroethyl) amino-L-phenylalanine derivative with carrier amino acids. In vivo bioassay. Cancer Chemother Pharmacol 12: 77–82
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This work is partially supported by: Ministero della Pubblica Istruzione, Roma, Italy, Fondi 40%.
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Gherlinzoni, F., Mazza, P., Zinzani, P.L. et al. Phase II cooperative study with a new alkylating drug, PTT-119, in the treatment of non-Hodgkin's lymphomas. Blut 60, 172–176 (1990). https://doi.org/10.1007/BF01720271
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DOI: https://doi.org/10.1007/BF01720271