The case records of patients under the care of one clinician (BJC) were carefully reviewed and those with a survival of ≥3 years from the date of diagnosis of metastatic disease were identified. Treatment modalities and event timelines were recorded and investigated for each patient. For the purposes of the study, data collection was ceased in April 2013. The literature was surveyed using PubMed and other databases for published clinical trials of agents that have been successfully used for the systemic treatment of metastatic melanoma from 1984. Search terms included: “metastatic melanoma”; “advanced melanoma”; “systemic therapy”; “complete response”; “CR”; “chemotherapy”; “DTIC”; “dacarbazine”; “temozolomide”; “fotemustine”; “IL-2”; “interleukin-2”; “pathway inhibitors”; “immunotherapy”; “vaccine”; “B-raf”; “Braf”; “CTLA-4”; and “PD-1”. Reported studies that utilized chemotherapy and other therapies for the treatment of advanced or metastatic melanoma were identified and included.
The median age was 55 years at melanoma presentation, with ages ranging from 33 to 83 years. The median duration of survival from the initial diagnosis of primary melanoma was 13.5 years. All individuals were Caucasian. Fourteen were male and three were female. American Joint Committee on cancer (AJCC) staging determined that there were 12 cases with stage IV and six with advanced stage III disease present at the time of initial therapy or observation. At the time of data collection closure, 18 patients were identified who had survived for ≥3 years after the diagnosis of advanced melanoma, ranging from 3 to 15 years in duration. Seventeen patients (94%) had survived 5 years or more and eleven patients (61%) had survived 10 years or more.
The median survival duration with metastatic disease was 11 years. At evaluation, 15 remained alive and three were dead (Table 1).
(To view a larger version of Table 1, click here.)
Detailed case series
Case A (Status: alive and disease-free; survival: 11 years)
A 48-year-old male presented in 1999 for WLE of a left paraumbilical melanoma, Clark level III, Breslow 0.95 mm. The patient remained disease-free for 2 years, until left groin metastatic melanoma nodal enlargement occurred in late 2001, and a left pelvic and inguinal nodal dissection was performed. The patient commenced a Phase III Canvaxin or Cancer Vax (C-Vax) trial for resected stage III melanoma in 2002; however, in June 2002, a solitary left cerebellar metastasis developed. This was treated with surgical resection and adjuvant whole-brain radiotherapy, and he was changed to the stage IV C-Vax trial protocol. In 2003, a splenectomy for multiple metastases was performed and the patient was then reinduced with C-Vax vaccine. Subsequent to C-Vax trial closure in April 2005, two cerebral nodules developed and were managed with surgical and stereotactic radiosurgical treatment. In 2006, radical right inguinal and pelvic nodal dissection for further metastases was performed. Later in 2006, WLE of a left buttock metastasis was performed. In 2007, the patient underwent palliative radiotherapy for a right sixth rib metastatic deposit. A left buttock recurrence occurred in January 2008 and vaccinia melanoma cell lysate (VMCL) vaccine trial therapy was commenced.
Case B (Status: alive and disease-free; survival: 7 years)
A 64-year-old female presented in early 2003 for WLE of melanoma of her left foot, Clark level IV, Breslow 2.2 mm, and subsequent radical left inguinal dissection. She remained disease-free until February 2006, when large pigmented nodules over the anterior aspect of her lower left leg were detected. Isolated limb infusion chemotherapy was performed in April 2006, with good initial control, but she experienced four further episodes of local cutaneous/subcutaneous recurrences over 1.5 years, treated surgically. In March 2008, multiple nonresectable nodules developed over the thigh and leg, and VMCL vaccine trial therapy was commenced, which continued for 8 months. Subcutaneous metastases over her left medial thigh and left lower leg decreased notably in size. In December 2008, regrowth occurred, and a Rose Bengal (PV-10; Provectus Pharmaceuticals, Inc., Knoxville, TN, USA) trial therapy was commenced for 5 months with some initial effect, but deposits eventually grew and further nodules appeared. Further surgical resection of deep soft tissue limb metastases was performed in May 2009, and again in September. VMCL therapy was recommenced in September 2009, with some clinical effect. In November 2009, left inguinal, external iliac, and common iliac lymphadenopathy developed. In January 2010, positron emission tomography (PET) imaging revealed progression of disease with abnormal fluorodeoxyglucose uptake in several retroperitoneal lymph nodes and further local subcutaneous metastases in her left leg. She was commenced on a “timed” schedule of VMCL vaccine therapy synchronized with immune fluctuations identified by monitoring high-sensitivity C-reactive protein levels, and similarly synchronized with dacarbazine (DTIC) chemotherapy in February 2010. Some stability of disease resulted (with regression of an enlarged high left inguinal lymph node) until April 2010, when disease progression was evident. In May 2010, “palliative” left radical high pelvic retroperitoneal lymph node dissection was performed. The combined timed vaccine and chemotherapy regimen was recommenced, until DTIC was ceased in December 2010 due to bone marrow suppression and low blood counts. All metastases regressed completely and repeated regular computed tomography (CT) scans have revealed no evidence of metastatic disease since.