CORRESPONDENCE Case Report: Development of Hodgkin's Disease in Patient Receiving Long-Term Administration of Dacarbazine and Interleukin-2 for Metastatic Melanoma
After the patient gave her informed consent, she was entered in an investigational treatment protocol. Dacarbazine (1.0 g/m2) on day 1 as a 24-hour continuous infusion and Interleukin-2 (IL-2)
1360
As more patients with metastatic melanoma are successfully treated with chemotherapy and immunotherapy, either alone or in combination, the possibility of developing a second malignancy exists. Physicians should be vigilant for that possibility. LAWRENCE E. FLAHERTY*
Division of Hematology and Oncology Wayne State University School of Medicine Detroit, Mich ROBERT SCHWERT
Department of Medicine Michigan State University E. Lansing, Mich BRUCE G. REDMAN
Division of Hematology and Oncology Wayne State University School of Medicine Detroit, Mich
References (/) COSTANZI JJ: DT1C (NSC-45388) Studies in the Southwest Oncology Group. Cancer Treat Rep 60:189-192, 1976 (2) ROSENBERG SA, LOTZE MT, MUUL LM: A
progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high dose interleukin-2 alone. N Engl J Med 316: 889-897, 1987 (3) ALLISON MA, JONES SE, MCGUFFEY P: Phase
II trial of outpatient interleukin-2 in malignant lymphoma, chronic lymphocytic leukemia, and selected solid tumors. J Clin Oncol 7:75-80, 1989 (4) Hsu S, YANG K, JAFFE ES: Phenotypic expres-
sion of Hodgkin's and Reed-Sternberg cells in Hodgkin's disease. Am J Pathol 118:209-217, 1985
*Correspondence to: Lawrence E. Flaherty, M.D., Division of Hematology and Oncology, Wayne State University School of Medicine, P.O. Box 02188, Detroit, MI 48202-0188.
Journal of the National Cancer Institute
Downloaded from http://jnci.oxfordjournals.org/ at Carleton University on June 16, 2015
In June 1985, a 31-year-old white female presented with a primary cutaneous malignant melanoma in the right lower quadrant of the abdominal wall. Primary excision and closure were performed. In March 1987, a solitary right inguinal lymph node metastasis was found during dissection, but no additional metastasis was observed during staging evaluation. However, in August 1987, biopsies of multiple, pigmented, subcutaneous lesions in the lower abdominal wall demonstrated metastatic melanoma, and a computerized tomography (CT) scan of the abdomen showed extensive liver metastases. CT scans of the brain and chest were normal. The liver was 12 cm in diameter and mildly tender; the lactate dehydrogenase (LDH) level was 1,320 U/L.
(18.0 x 106IU/m2) by intravenous bolus over 15 minutes on days 15-19 and days 22-26 were administered every 28 days. After two courses of therapy, a CT scan showed partial remission of the liver metastases and the LDH level returned to 140 U/L. A permanent dose reduction of the IL-2 (12.0 x 106 IU/m2) during course 5 was necessary because the patient experienced moderate depression and arthralgia. After 15 months of therapy, the protocol was extended from 28 days to 42 days with 2 additional weeks off after IL-2. CT scans of the abdomen, which were repeated every 3-4 months, documented a persistent partial remission. In August 1989, after completing 2 full years of therapy, skin and open-liver biopsies demonstrated persistent partial remission. Treatment continued, and on January 2, 1990, a biopsy of a new left supraclavicular node revealed nodular sclerosing Hodgkin's disease. CT scans of the abdomen demonstrated persistent, stable liver metastases, and bilateral bone marrow biopsies revealed no tumor. However, a CT scan of the chest showed a new anterior mediastinal mass (diameter, 4.0 cm), which was diagnosed as clinical stage IIA Hodgkin's disease. The patient was treated with a course of mantle radiation therapy. The patient remains in partial remission of both metastatic melanoma and Hodgkin's disease and is not presently receiving therapy. Dacarbazine and IL-2 are known active agents in the management of both metastatic melanoma and Hodgkin's disease (1-3). To date, there is no known association between their administration and the development of second malignancies. There is also no known association between metastatic melanoma and the development of Hodgkin's disease. This lack of association is probably related to the short survival time for patients developing metastatic melanoma. The cellular origin of Hodgkin's disease has not been firmly established. ReedSternberg cells do express antigens of activated B or T cells as well as IL-2^ receptors (4). Whether the long-term administration of IL-2, dacarbazine, or a combination of the two may have a role in the development of Hodgkin's disease is unclear.
After the patient gave her informed consent, she was entered in an investigational treatment protocol. Dacarbazine (1.0 g/m2) on day 1 as a 24-hour continuous infusion and Interleukin-2 (IL-2)
1360
As more patients with metastatic melanoma are successfully treated with chemotherapy and immunotherapy, either alone or in combination, the possibility of developing a second malignancy exists. Physicians should be vigilant for that possibility. LAWRENCE E. FLAHERTY*
Division of Hematology and Oncology Wayne State University School of Medicine Detroit, Mich ROBERT SCHWERT
Department of Medicine Michigan State University E. Lansing, Mich BRUCE G. REDMAN
Division of Hematology and Oncology Wayne State University School of Medicine Detroit, Mich
References (/) COSTANZI JJ: DT1C (NSC-45388) Studies in the Southwest Oncology Group. Cancer Treat Rep 60:189-192, 1976 (2) ROSENBERG SA, LOTZE MT, MUUL LM: A
progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high dose interleukin-2 alone. N Engl J Med 316: 889-897, 1987 (3) ALLISON MA, JONES SE, MCGUFFEY P: Phase
II trial of outpatient interleukin-2 in malignant lymphoma, chronic lymphocytic leukemia, and selected solid tumors. J Clin Oncol 7:75-80, 1989 (4) Hsu S, YANG K, JAFFE ES: Phenotypic expres-
sion of Hodgkin's and Reed-Sternberg cells in Hodgkin's disease. Am J Pathol 118:209-217, 1985
*Correspondence to: Lawrence E. Flaherty, M.D., Division of Hematology and Oncology, Wayne State University School of Medicine, P.O. Box 02188, Detroit, MI 48202-0188.
Journal of the National Cancer Institute
Downloaded from http://jnci.oxfordjournals.org/ at Carleton University on June 16, 2015
In June 1985, a 31-year-old white female presented with a primary cutaneous malignant melanoma in the right lower quadrant of the abdominal wall. Primary excision and closure were performed. In March 1987, a solitary right inguinal lymph node metastasis was found during dissection, but no additional metastasis was observed during staging evaluation. However, in August 1987, biopsies of multiple, pigmented, subcutaneous lesions in the lower abdominal wall demonstrated metastatic melanoma, and a computerized tomography (CT) scan of the abdomen showed extensive liver metastases. CT scans of the brain and chest were normal. The liver was 12 cm in diameter and mildly tender; the lactate dehydrogenase (LDH) level was 1,320 U/L.
(18.0 x 106IU/m2) by intravenous bolus over 15 minutes on days 15-19 and days 22-26 were administered every 28 days. After two courses of therapy, a CT scan showed partial remission of the liver metastases and the LDH level returned to 140 U/L. A permanent dose reduction of the IL-2 (12.0 x 106 IU/m2) during course 5 was necessary because the patient experienced moderate depression and arthralgia. After 15 months of therapy, the protocol was extended from 28 days to 42 days with 2 additional weeks off after IL-2. CT scans of the abdomen, which were repeated every 3-4 months, documented a persistent partial remission. In August 1989, after completing 2 full years of therapy, skin and open-liver biopsies demonstrated persistent partial remission. Treatment continued, and on January 2, 1990, a biopsy of a new left supraclavicular node revealed nodular sclerosing Hodgkin's disease. CT scans of the abdomen demonstrated persistent, stable liver metastases, and bilateral bone marrow biopsies revealed no tumor. However, a CT scan of the chest showed a new anterior mediastinal mass (diameter, 4.0 cm), which was diagnosed as clinical stage IIA Hodgkin's disease. The patient was treated with a course of mantle radiation therapy. The patient remains in partial remission of both metastatic melanoma and Hodgkin's disease and is not presently receiving therapy. Dacarbazine and IL-2 are known active agents in the management of both metastatic melanoma and Hodgkin's disease (1-3). To date, there is no known association between their administration and the development of second malignancies. There is also no known association between metastatic melanoma and the development of Hodgkin's disease. This lack of association is probably related to the short survival time for patients developing metastatic melanoma. The cellular origin of Hodgkin's disease has not been firmly established. ReedSternberg cells do express antigens of activated B or T cells as well as IL-2^ receptors (4). Whether the long-term administration of IL-2, dacarbazine, or a combination of the two may have a role in the development of Hodgkin's disease is unclear.
