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Ten-year survival in advanced malignant melanoma following treatment with interferon and vindesine
Annals of Oncology 11: 483-485, 2000. © 2000 Kluwer Academic Publishers. Primed in the Netherlands
Clinical case Ten-year survival in advanced malignant melanoma following treatment with interferon and vindesine M. Iqbal, E. Marshall & J. A. Green Clatlerbridge centrefor Oncology, Clatterbridge, Bebington, Wirral, UK
A 31-year-old man with malignant melanoma of his right popliteal fossa was treated in 1987 with surgical excision followed by local radiotherapy. Eight months later, he presented with recurrence in the right inguinal lymph nodes, which were resected and followed by radiotherapy to the groin. Ten months later, he developed liver metastases and was treated with vinde-
Introduction
Throughout the world the incidence of cutaneous melanoma in Caucasians is rising more rapidly than any other solid tumor with rates of 40 per 100,000 reported in Queensland, Australia [1]. The majority of patients still present with early cutaneous disease at a time when cure remains a realistic goal of therapy and indeed mortality rates have remained stable despite the greater incidence. In marked contrast, metastatic disease carries a grave prognosis and to date, neither chemotherapy nor biological therapy has had a significant impact on survival. Median survival of patients with advanced disease is only in the region of four to six months although a subgroup of patients with predominantly soft tissue or lung disease appears to show a more favorable response to treatment. The presence of liver involvement signifies a particularly poor prognosis in melanoma with median survival of usually less than six months [2]. This paper describes the characteristics of a longterm survivor with melanoma who is alive and well 10 years after the development of extensive liver metastases. To the best of our knowledge, this has not been reported before. Case report A 31-year-old male Caucasian presented in September 1987 with a superficial melanoma arising from the right popliteal fossa. Complete excision was followed by postoperative radiotherapy (45 Gy electrons in 10 fractions over 14 days). Eight months later he presented with regional lymphadenopathy and underwent a limited in-
sine (12 months) and interferon-a-2a (30 months) resulting in complete remission which has been maintained for over 10 years. This interesting case report, with brief review of literature, is presented here.
Key words: interferon, liver metastases, malignant melanoma, vindesine
guinal node dissection for histologically confirmed recurrence followed by locoregional radiotherapy (25 Gy in 10 fractions over 14 days). One year later he developed right hypochondrial pain and tender hepatomegaly with abnormal liver function tests - lactic dehydrogenase 1306 iu/1 (normal limit 230-480 iu/1), aspartate aminotransaminase 55 iu/1 (normal 0-40) and alanine aminotransaminase (ALT) 67 iu/1 (normal 0-40). Ultrasound examination of the upper abdomen revealed multiple hypoechoic lesions consistent with liver metastases and these abnormalities were confirmed on CT scan examination with the largest lesion measuring 4.7 cm (see Figure 1). Liver biopsy was not carried out in view of the clinical presentation and radiological findings. In April 1989 he commenced combination therapy with vindesine and interferon-a-2a as part of phase II study [3]. Vindesine (3 mg/m2) was administered intravenously every 21 days and interferon was given concomitantly at a starting dose of 3MU subcutaneously on alternate days, escalating to 9 mu subcutaneously daily after 21 days. Over a period of three to four months his clinical condition improved with resolution of the tender hepatomegaly and normalization of his liver function tests. CT examination of his liver at four-monthly intervals revealed stable disease at one year at which point his vindesine therapy was stopped. CT examination at 18 months revealed a delayed response to treatment with a dramatic reduction in the liver disease and at this point the interferon dose was reduced but he continued on a maintenance dose of 3 mu three times per week. CT scanning of his liver at year 2 showed a complete response (Figure 2). Interferon was discontinued after 30 months in the absence of data on long-term treatment. The agent was generally well tolerated, self-adminis-
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Summary
484
Discussion Metastatic melanoma is typically associated with a poor prognosis and limited response to treatment, although
References 1. Glass AG, Hoover RN. The emerging epidemic of melanoma and squamous cell skin cancer. JAMA 1989; 262: 2097—100.
Downloaded from https://academic.oup.com/annonc/article-abstract/11/4/483/205369 by guest on 04 February 2019
its behavior may vary significantly from patient to patient. Furthermore melanoma is one of only several cancers where spontaneous remissions have been documented. Ten to twenty-five percent of patients develop liver metastases during the course of their illness although the true incidence is probably far greater as judged by postmortem examination findings [2, 4, 5]. In the setting of widely disseminated disease, the prognosis for patients with liver involvement is particularly poor with a median survival of less than six months. Unfortunately, systemic therapy for advanced melanoma has had little impact on overall survival. Most responses have been sporadic, unpredictable and short lived although l%-2% of patients may achieve durable responses to biological therapy, most notably those presenting with skin, subcutaneous tissue, lymph nodes or lung [6,7]. Malignant melanoma, even in its advanced stage, can be associated with spontaneous regression, but this is rare. Reported incidence varies in different studies, but probably occurs in less than 0.5% of cases [8, 9]. Where spontaneous remission has been reported this almost always occurs in patients with cutaneous or lymph node disease or following surgical resection of metastases. The Mayo clinic reported its experience of long-term survivors in 503 patients who had entered clinical trials between 1971-1984 [10]. Of these individuals three patients who achieved a complete remission and seven patients who achieved a partial remission after systemic therapy were considered as long-term survivors (6.1-14.7 Figure 1. (a) and (b) CTscan at the time of diagnosis of liver metastasis. years). Six patients were alive after 14.7 years, of which four patients presented with local cutaneous disease or lymph node involvement, one patient had pulmonary metastases and the final patient had complete resection of a splenic metastasis. Petit et al. [7] identified 7 longterm survivors in a phase II study of fotemustine in 169 patients. All were rendered disease free with surgery following cytotoxic treatment. Finally, Nathanson [8] cited 27 cases of spontaneous remission in a literature review on the subject published in 1974. Patients with cutaneous disease predominated but four cases of possible liver disease were highlighted of which two were considered doubtful and no long-term follow up was available for the other two. The patient described presented with rapidly progressive disease with lymph node and liver involvement within 18 months of original diagnosis. While histologFigure 2. CT scan showing complete resolution of liver metastasis. ical confirmation was not obtained, we contend the clinical, biochemical and radiological appearances are tered and did not interfere with quality of life as he diagnostic. The clinical response to systemic therapy was maintained a fulltime job. It is now over 10 years since swift but radiological response was delayed, a phenomenhis first relapse and he remains disease free and clini- on that has been well described with interferon although cally well. most responses occur within three months [11].
485 9. O'Connell MEA, Powell BWEM, Connell JM et al. Spontaneous regression of multiple bone metastasis in malignant melanoma. Br J Radiol 1989; 62: 1095-100 10. Ahmann DL, Cregon ET, Hahnet RG et al. Complete responses and long term survivor after systemic chemotherapy for patients with advanced malignant melanoma. Cancer 1989; 63: 224-7. 11. Biological therapy with interferon-alpha and beta: Clinical applications: Melanoma. In DeVita VT, Hellman S, Rosenberg SA (eds): Biological Therapy of Cancer: Principal and Practice of Oncology. Philadelphia: JB Lippincot 1995; 388. Received 29 March 1999; accepted 6 April 1999. Correspondence to: J. A. Green, MD Clatterbridge Centre for Oncology Clatterbridge, Bebington Wirral, L63 5JY UK
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2. Balch CM, Soong SJ, Morris TM et al. A multifactorial analysis of melanoma in prognostic factors in 200 melanoma patients with distant metastasis (stage III). J Clin Oncol 1983; 1 (2): 126-34. 3. Smith KA, Green JA, Eccles JM. Interferon-ct-2a and vindesine in the treatment of advanced malignant melanoma. Eur J Cancer 1992; 28 (2/3): 438-41. 4. Amer MH, Al-Sharref M, Vaitrevicius VK. Clinical presentation. Natural history and prognostic factor in advanced melanoma. Surg Gynecol Obstet 1979; 149 (5); 687-92. 5. Das Gupta T, Brasfield R. Metastatic melanoma: A clinicopathological study. Cancer 1964; 17:1323—39. 6. Coates AS, Segelow V. Long-term responses to chemotherapy in patients with visceral metastasis. Ann Oncol 1984; 5: 249-51. 7. Petit T, Borel C, Rixe O et al. Complete remission seven years after treatment for metastatic malignant melanoma. Cancer 1986; 77: 900-2. 8. Nathanson L. Spontaneous regression of malignant melanoma: A review of the literature on incidence, clinical factor and possible mechanism. Conference on spontaneous regression of Cancer. NCJ Monogr 1976; 44: 67-77.
Downloaded from https://academic.oup.com/annonc/article-abstract/11/4/483/205369 by guest on 04 February 2019
Clinical case Ten-year survival in advanced malignant melanoma following treatment with interferon and vindesine M. Iqbal, E. Marshall & J. A. Green Clatlerbridge centrefor Oncology, Clatterbridge, Bebington, Wirral, UK
A 31-year-old man with malignant melanoma of his right popliteal fossa was treated in 1987 with surgical excision followed by local radiotherapy. Eight months later, he presented with recurrence in the right inguinal lymph nodes, which were resected and followed by radiotherapy to the groin. Ten months later, he developed liver metastases and was treated with vinde-
Introduction
Throughout the world the incidence of cutaneous melanoma in Caucasians is rising more rapidly than any other solid tumor with rates of 40 per 100,000 reported in Queensland, Australia [1]. The majority of patients still present with early cutaneous disease at a time when cure remains a realistic goal of therapy and indeed mortality rates have remained stable despite the greater incidence. In marked contrast, metastatic disease carries a grave prognosis and to date, neither chemotherapy nor biological therapy has had a significant impact on survival. Median survival of patients with advanced disease is only in the region of four to six months although a subgroup of patients with predominantly soft tissue or lung disease appears to show a more favorable response to treatment. The presence of liver involvement signifies a particularly poor prognosis in melanoma with median survival of usually less than six months [2]. This paper describes the characteristics of a longterm survivor with melanoma who is alive and well 10 years after the development of extensive liver metastases. To the best of our knowledge, this has not been reported before. Case report A 31-year-old male Caucasian presented in September 1987 with a superficial melanoma arising from the right popliteal fossa. Complete excision was followed by postoperative radiotherapy (45 Gy electrons in 10 fractions over 14 days). Eight months later he presented with regional lymphadenopathy and underwent a limited in-
sine (12 months) and interferon-a-2a (30 months) resulting in complete remission which has been maintained for over 10 years. This interesting case report, with brief review of literature, is presented here.
Key words: interferon, liver metastases, malignant melanoma, vindesine
guinal node dissection for histologically confirmed recurrence followed by locoregional radiotherapy (25 Gy in 10 fractions over 14 days). One year later he developed right hypochondrial pain and tender hepatomegaly with abnormal liver function tests - lactic dehydrogenase 1306 iu/1 (normal limit 230-480 iu/1), aspartate aminotransaminase 55 iu/1 (normal 0-40) and alanine aminotransaminase (ALT) 67 iu/1 (normal 0-40). Ultrasound examination of the upper abdomen revealed multiple hypoechoic lesions consistent with liver metastases and these abnormalities were confirmed on CT scan examination with the largest lesion measuring 4.7 cm (see Figure 1). Liver biopsy was not carried out in view of the clinical presentation and radiological findings. In April 1989 he commenced combination therapy with vindesine and interferon-a-2a as part of phase II study [3]. Vindesine (3 mg/m2) was administered intravenously every 21 days and interferon was given concomitantly at a starting dose of 3MU subcutaneously on alternate days, escalating to 9 mu subcutaneously daily after 21 days. Over a period of three to four months his clinical condition improved with resolution of the tender hepatomegaly and normalization of his liver function tests. CT examination of his liver at four-monthly intervals revealed stable disease at one year at which point his vindesine therapy was stopped. CT examination at 18 months revealed a delayed response to treatment with a dramatic reduction in the liver disease and at this point the interferon dose was reduced but he continued on a maintenance dose of 3 mu three times per week. CT scanning of his liver at year 2 showed a complete response (Figure 2). Interferon was discontinued after 30 months in the absence of data on long-term treatment. The agent was generally well tolerated, self-adminis-
Downloaded from https://academic.oup.com/annonc/article-abstract/11/4/483/205369 by guest on 04 February 2019
Summary
484
Discussion Metastatic melanoma is typically associated with a poor prognosis and limited response to treatment, although
References 1. Glass AG, Hoover RN. The emerging epidemic of melanoma and squamous cell skin cancer. JAMA 1989; 262: 2097—100.
Downloaded from https://academic.oup.com/annonc/article-abstract/11/4/483/205369 by guest on 04 February 2019
its behavior may vary significantly from patient to patient. Furthermore melanoma is one of only several cancers where spontaneous remissions have been documented. Ten to twenty-five percent of patients develop liver metastases during the course of their illness although the true incidence is probably far greater as judged by postmortem examination findings [2, 4, 5]. In the setting of widely disseminated disease, the prognosis for patients with liver involvement is particularly poor with a median survival of less than six months. Unfortunately, systemic therapy for advanced melanoma has had little impact on overall survival. Most responses have been sporadic, unpredictable and short lived although l%-2% of patients may achieve durable responses to biological therapy, most notably those presenting with skin, subcutaneous tissue, lymph nodes or lung [6,7]. Malignant melanoma, even in its advanced stage, can be associated with spontaneous regression, but this is rare. Reported incidence varies in different studies, but probably occurs in less than 0.5% of cases [8, 9]. Where spontaneous remission has been reported this almost always occurs in patients with cutaneous or lymph node disease or following surgical resection of metastases. The Mayo clinic reported its experience of long-term survivors in 503 patients who had entered clinical trials between 1971-1984 [10]. Of these individuals three patients who achieved a complete remission and seven patients who achieved a partial remission after systemic therapy were considered as long-term survivors (6.1-14.7 Figure 1. (a) and (b) CTscan at the time of diagnosis of liver metastasis. years). Six patients were alive after 14.7 years, of which four patients presented with local cutaneous disease or lymph node involvement, one patient had pulmonary metastases and the final patient had complete resection of a splenic metastasis. Petit et al. [7] identified 7 longterm survivors in a phase II study of fotemustine in 169 patients. All were rendered disease free with surgery following cytotoxic treatment. Finally, Nathanson [8] cited 27 cases of spontaneous remission in a literature review on the subject published in 1974. Patients with cutaneous disease predominated but four cases of possible liver disease were highlighted of which two were considered doubtful and no long-term follow up was available for the other two. The patient described presented with rapidly progressive disease with lymph node and liver involvement within 18 months of original diagnosis. While histologFigure 2. CT scan showing complete resolution of liver metastasis. ical confirmation was not obtained, we contend the clinical, biochemical and radiological appearances are tered and did not interfere with quality of life as he diagnostic. The clinical response to systemic therapy was maintained a fulltime job. It is now over 10 years since swift but radiological response was delayed, a phenomenhis first relapse and he remains disease free and clini- on that has been well described with interferon although cally well. most responses occur within three months [11].
485 9. O'Connell MEA, Powell BWEM, Connell JM et al. Spontaneous regression of multiple bone metastasis in malignant melanoma. Br J Radiol 1989; 62: 1095-100 10. Ahmann DL, Cregon ET, Hahnet RG et al. Complete responses and long term survivor after systemic chemotherapy for patients with advanced malignant melanoma. Cancer 1989; 63: 224-7. 11. Biological therapy with interferon-alpha and beta: Clinical applications: Melanoma. In DeVita VT, Hellman S, Rosenberg SA (eds): Biological Therapy of Cancer: Principal and Practice of Oncology. Philadelphia: JB Lippincot 1995; 388. Received 29 March 1999; accepted 6 April 1999. Correspondence to: J. A. Green, MD Clatterbridge Centre for Oncology Clatterbridge, Bebington Wirral, L63 5JY UK
Downloaded from https://academic.oup.com/annonc/article-abstract/11/4/483/205369 by guest on 04 February 2019
2. Balch CM, Soong SJ, Morris TM et al. A multifactorial analysis of melanoma in prognostic factors in 200 melanoma patients with distant metastasis (stage III). J Clin Oncol 1983; 1 (2): 126-34. 3. Smith KA, Green JA, Eccles JM. Interferon-ct-2a and vindesine in the treatment of advanced malignant melanoma. Eur J Cancer 1992; 28 (2/3): 438-41. 4. Amer MH, Al-Sharref M, Vaitrevicius VK. Clinical presentation. Natural history and prognostic factor in advanced melanoma. Surg Gynecol Obstet 1979; 149 (5); 687-92. 5. Das Gupta T, Brasfield R. Metastatic melanoma: A clinicopathological study. Cancer 1964; 17:1323—39. 6. Coates AS, Segelow V. Long-term responses to chemotherapy in patients with visceral metastasis. Ann Oncol 1984; 5: 249-51. 7. Petit T, Borel C, Rixe O et al. Complete remission seven years after treatment for metastatic malignant melanoma. Cancer 1986; 77: 900-2. 8. Nathanson L. Spontaneous regression of malignant melanoma: A review of the literature on incidence, clinical factor and possible mechanism. Conference on spontaneous regression of Cancer. NCJ Monogr 1976; 44: 67-77.
Downloaded from https://academic.oup.com/annonc/article-abstract/11/4/483/205369 by guest on 04 February 2019