Cancer Investigation
ISSN: 0735-7907 (Print) 1532-4192 (Online) Journal homepage: http://www.tandfonline.com/loi/icnv20
Phase II Trial of Methyl-gag and Melphalan in Metastatic Adult Renal Cell Carcinoma Jose-Luis Guimaraes, Marwane Ghosn, Maurizio Ostronoff, Mohamed Azab, Christine Theodore & Jean-Pierre Droz To cite this article: Jose-Luis Guimaraes, Marwane Ghosn, Maurizio Ostronoff, Mohamed Azab, Christine Theodore & Jean-Pierre Droz (1990) Phase II Trial of Methyl-gag and Melphalan in Metastatic Adult Renal Cell Carcinoma, Cancer Investigation, 8:6, 623-624, DOI: 10.3109/07357909009018930 To link to this article: http://dx.doi.org/10.3109/07357909009018930
Published online: 11 Jun 2009.
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Article views: 1
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=icnv20 Download by: [137.189.171.235]
Date: 14 June 2016, At: 15:24
Cancer Investigation, 8(6) 623-624 (1990)
Phase I1 Trial of Methyl-gag and Melphalan in Metastatic Adult Renal Cell Carcinoma
Downloaded by [] at 15:24 14 June 2016
Jose-Luis Guimaraes, M.D., Marwane Ghosn, M.D., Maurizio Ostronoff, M.D., Mohamed Azab, M.D., Christine Theodore, M.D., and Jean-Pierre Droz M.D. Medical Department lnstitut Gustave-Roussy Villejuif, France
ABSTRACT
A trial of melphalan and methyl-gag was undertaken in 16patients with metastatic renal cell carcinoma. Among 14 evaluable patients, 6 had stabilization of disease. No significantresponses were observed. While both drugs have produced occasional responses in renal cancer, their combination shows no therapeutic advantage.
Melphalan (L-phenylalanine mustard/L-PAM) is a bifunctional alkylating agent commonly administered orally (1). Methyl-gag (methyl-glyoxal-bis-guanylhydrazone) is an inhibitor of polyamine biosynthesis (2-4). Both drugs have shown occasional responses in renal cancers, although the possible role of intravenous melphalan has not been well defined (1,4). Myelotoxicity is usually the limiting toxicity of melphalan, where as this toxicity is practically absent with methyl-gag (1,4). Between September 1, 1987 and November 30, 1988, 16 patients with measurable metastatic renal cell carcinoma were entered in a Phase II trial of methylgaglmelphalan association. Patient characteristics are listed in Table 1. Methyl-gag was given at a dose of 500 mg/m2 in 1 L of 10% dextrose in water in a 3-h perfusion on Days 1, 8,22, and 29. Melphalan 0.5 mg/kg was given in 250 ml 623 Copyright @ 1991 by Marcel Dekker, Inc.
of 9 % saline solution in a 30-min perfusion on Day 1. This treatment was repeated on Day 42. The tumor response was assessed according to the World Health Organization response criteria at least 3 weeks after the administration of two cycles of therapy ( 5 ) . Two patients were lost for follow-up after Day 8 of treatment. In the remaining 14 patients no response was observed. Only six patients had stabilization of their disease. Except for two patients who had a short, rapidly resolving aplasia, no life-threatening toxic effects were noted during the treatment. Gastrointestinal toxicity (mucositis and diarrhea) occurred in 4 patients. Our results are in accordance with what is actually known of the high resistance of renal carcinoma to conventional attempts of chemotherapy (5). Twelve of these 16 patients had a very poor prognosis according to our predictive survival rate function (6). We feel that future
Guimaraes et al.
624
protocols shouldbe addressed to more specific subgroups of patients in order to identify more active treatments.
Table 1 Patient Characteristics Characteristic Total Evaluable Sex: Male Female Median age in years (range): 57.4 (29-72) Performance status
Downloaded by [] at 15:24 14 June 2016
0- 1
2-3 Initial nephrectomy Disease-free interval (months) 0 0-18 18 Site of metastatic disease Lung Lymph nodes Bone Liver Other Prior therapy for metastasis None Chemotherapy Radiotherapy Hormonal therapy Toxic effects Nausea and vomiting Mucositis Diarrhea Cholestasis Aplasia Myalgia
No. of Patients 16 14 11
5 12 4 8
11 3 2 12 3 7 2 4
6 5 4
1 8
4 3 3 2 1
ACKNOWLEDGMENTS We thank Mrs. M. Belleteste for her secretarial help in the preparation of the manuscript.
Address reprint requests to: J.P. Droz, M.D., Institut Gustave-Roussy, Rue Camille Desmoulins, 94800 Villejuif, France.
REFERENCES 1. Sarosy G, Leylarrl-Jones B, Cheson B D The systemic administration of intravenous mlphalan. J Clin Oncol 6:1768-1782, 1988. 2. Knight W, Livingston R, Fabian D et al: Phase I-II trial of methylgag: A Southwest Oncology Group pilot study. Cancer Treat Rep 63~1933-1937, 1979. 3. Todd F, Garnick M,Canellos G et al: Phase I-II trial of methylgag in the treatment of patients with metastatic renal adenocarcinoma. Cancer Treat Rep 6517-20, 1981. 4. Zeffren J, Yagoda A, Watson R et al: Phase I-II trial of methylgag in advanced renal cancer. Cancer Treat Rep 65525-527, 1981. 5 . Miller AB, Hoogstraten B, Staquet M et al: Reporting results of cancer treatment. Cancer 47:207-214, 1981. 6. Droz JP, Theodore C, Ghosn M et al: Twelve year experience with chemotherapyin adult metastatic renal cell carcinomaat the Institut Gustave-Roussy. Sem Surg Oncol 4:97-99, 1988. 7. De Forges A, Rey A, Klink M et al: Prognostic factors of adult metastatic renal carcinoma: a multivariate analysis. Sem Surg Oncol 4: 149-154, 1988.
ISSN: 0735-7907 (Print) 1532-4192 (Online) Journal homepage: http://www.tandfonline.com/loi/icnv20
Phase II Trial of Methyl-gag and Melphalan in Metastatic Adult Renal Cell Carcinoma Jose-Luis Guimaraes, Marwane Ghosn, Maurizio Ostronoff, Mohamed Azab, Christine Theodore & Jean-Pierre Droz To cite this article: Jose-Luis Guimaraes, Marwane Ghosn, Maurizio Ostronoff, Mohamed Azab, Christine Theodore & Jean-Pierre Droz (1990) Phase II Trial of Methyl-gag and Melphalan in Metastatic Adult Renal Cell Carcinoma, Cancer Investigation, 8:6, 623-624, DOI: 10.3109/07357909009018930 To link to this article: http://dx.doi.org/10.3109/07357909009018930
Published online: 11 Jun 2009.
Submit your article to this journal
Article views: 1
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=icnv20 Download by: [137.189.171.235]
Date: 14 June 2016, At: 15:24
Cancer Investigation, 8(6) 623-624 (1990)
Phase I1 Trial of Methyl-gag and Melphalan in Metastatic Adult Renal Cell Carcinoma
Downloaded by [] at 15:24 14 June 2016
Jose-Luis Guimaraes, M.D., Marwane Ghosn, M.D., Maurizio Ostronoff, M.D., Mohamed Azab, M.D., Christine Theodore, M.D., and Jean-Pierre Droz M.D. Medical Department lnstitut Gustave-Roussy Villejuif, France
ABSTRACT
A trial of melphalan and methyl-gag was undertaken in 16patients with metastatic renal cell carcinoma. Among 14 evaluable patients, 6 had stabilization of disease. No significantresponses were observed. While both drugs have produced occasional responses in renal cancer, their combination shows no therapeutic advantage.
Melphalan (L-phenylalanine mustard/L-PAM) is a bifunctional alkylating agent commonly administered orally (1). Methyl-gag (methyl-glyoxal-bis-guanylhydrazone) is an inhibitor of polyamine biosynthesis (2-4). Both drugs have shown occasional responses in renal cancers, although the possible role of intravenous melphalan has not been well defined (1,4). Myelotoxicity is usually the limiting toxicity of melphalan, where as this toxicity is practically absent with methyl-gag (1,4). Between September 1, 1987 and November 30, 1988, 16 patients with measurable metastatic renal cell carcinoma were entered in a Phase II trial of methylgaglmelphalan association. Patient characteristics are listed in Table 1. Methyl-gag was given at a dose of 500 mg/m2 in 1 L of 10% dextrose in water in a 3-h perfusion on Days 1, 8,22, and 29. Melphalan 0.5 mg/kg was given in 250 ml 623 Copyright @ 1991 by Marcel Dekker, Inc.
of 9 % saline solution in a 30-min perfusion on Day 1. This treatment was repeated on Day 42. The tumor response was assessed according to the World Health Organization response criteria at least 3 weeks after the administration of two cycles of therapy ( 5 ) . Two patients were lost for follow-up after Day 8 of treatment. In the remaining 14 patients no response was observed. Only six patients had stabilization of their disease. Except for two patients who had a short, rapidly resolving aplasia, no life-threatening toxic effects were noted during the treatment. Gastrointestinal toxicity (mucositis and diarrhea) occurred in 4 patients. Our results are in accordance with what is actually known of the high resistance of renal carcinoma to conventional attempts of chemotherapy (5). Twelve of these 16 patients had a very poor prognosis according to our predictive survival rate function (6). We feel that future
Guimaraes et al.
624
protocols shouldbe addressed to more specific subgroups of patients in order to identify more active treatments.
Table 1 Patient Characteristics Characteristic Total Evaluable Sex: Male Female Median age in years (range): 57.4 (29-72) Performance status
Downloaded by [] at 15:24 14 June 2016
0- 1
2-3 Initial nephrectomy Disease-free interval (months) 0 0-18 18 Site of metastatic disease Lung Lymph nodes Bone Liver Other Prior therapy for metastasis None Chemotherapy Radiotherapy Hormonal therapy Toxic effects Nausea and vomiting Mucositis Diarrhea Cholestasis Aplasia Myalgia
No. of Patients 16 14 11
5 12 4 8
11 3 2 12 3 7 2 4
6 5 4
1 8
4 3 3 2 1
ACKNOWLEDGMENTS We thank Mrs. M. Belleteste for her secretarial help in the preparation of the manuscript.
Address reprint requests to: J.P. Droz, M.D., Institut Gustave-Roussy, Rue Camille Desmoulins, 94800 Villejuif, France.
REFERENCES 1. Sarosy G, Leylarrl-Jones B, Cheson B D The systemic administration of intravenous mlphalan. J Clin Oncol 6:1768-1782, 1988. 2. Knight W, Livingston R, Fabian D et al: Phase I-II trial of methylgag: A Southwest Oncology Group pilot study. Cancer Treat Rep 63~1933-1937, 1979. 3. Todd F, Garnick M,Canellos G et al: Phase I-II trial of methylgag in the treatment of patients with metastatic renal adenocarcinoma. Cancer Treat Rep 6517-20, 1981. 4. Zeffren J, Yagoda A, Watson R et al: Phase I-II trial of methylgag in advanced renal cancer. Cancer Treat Rep 65525-527, 1981. 5 . Miller AB, Hoogstraten B, Staquet M et al: Reporting results of cancer treatment. Cancer 47:207-214, 1981. 6. Droz JP, Theodore C, Ghosn M et al: Twelve year experience with chemotherapyin adult metastatic renal cell carcinomaat the Institut Gustave-Roussy. Sem Surg Oncol 4:97-99, 1988. 7. De Forges A, Rey A, Klink M et al: Prognostic factors of adult metastatic renal carcinoma: a multivariate analysis. Sem Surg Oncol 4: 149-154, 1988.
