Systemic therapy of metastatic melanoma

1999 ◽  
Vol 56 (6) ◽  
pp. 330-333
Author(s):  
Dummer ◽  
Nestle ◽  
Hofbauer ◽  
Burg

Das metastasierende Melanom (MM) gehört zu den schwierig behandelbaren Malignomen, wobei Allgemeinzustand und Motivation des Patienten neben Zahl und Lokalisation der Metastasen das therapeutische Vorgehen bestimmen. Solitäre Metastasen in Lunge, ZNS, Weichteilen und Lymphknoten sollten primär chirurgisch entfernt werden. Multiple Metastasen, insbesondere abdominal, werden nur in Ausnahmefällen chirurgisch angegangen. Hier ist vielmehr ein systemische Chemoimmuntherapie angebracht. Aussichtsreiche Behandlungskonzepte beinhalten Interleukin-2, Interferon, und verschiedenen Zytostatika wie DTIC, Temozolamid, Vindesine oder Cisplatin. Bei ZNS- und Skelettfiliae ist die Radiotherapie einzusetzen. Durch diese Chemoimmuntherapien hat sich die Prognose des metastasierenden Melanoms bezüglich des Überlebens verbessert. Langfristig wird aber nur eine Kombination von zeitraubenden Multicenterstudien und experimentellen Ansätzen in der Lage sein, uns langsam an eine kurative Therapie heranzuführen.

2021 ◽  
Vol 69 (4) ◽  
pp. 888-892
Author(s):  
Joseph I Clark ◽  
Brendan Curti ◽  
Elizabeth J Davis ◽  
Howard Kaufman ◽  
Asim Amin ◽  
...  

High-dose interleukin-2 (HD IL-2) was approved in the 1990s after demonstrating durable complete responses (CRs) in some patients with metastatic melanoma (mM) and metastatic renal cell carcinoma (mRCC). Patients who achieve this level of disease control have also demonstrated improved survival compared with patients who progress, but limited data are available describing the long-term course. The aim of this study was to better characterize long-term survival following successful HD IL-2 treatment in patients with no subsequent systemic therapy. Eleven HD IL-2 treatment centers identified patients with survival ≥5 years after HD IL-2, with no subsequent systemic therapy. Survival was evaluated from the date of IL-2 treatment to June 2017. Treatment courses consisted of 2 1-week cycles of HD IL-2. Patients were treated with HD IL-2 alone, or HD IL-2 followed by local therapy to achieve maximal response. 100 patients are reported: 54 patients with mM and 46 patients with mRCC. Progression-free survival (PFS) after HD IL-2 ranges from 5+ years to 30+ years, with a median follow-up of 10+ years. 27 mRCC and 32 mM are alive ≥10 years after IL-2. Thus, a small subset of patients with mM and mRCC achieve long-term PFS (≥5 years) after treatment with HD IL-2 as their only systemic therapy. The ability of HD IL-2 therapy to induce prolonged PFS should be a major consideration in studies of new immunotherapy combinations for mM and mRCC.


2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e19043-e19043
Author(s):  
Zhongyun Zhao ◽  
Song Wang ◽  
Beth Barber ◽  
Volker Jean Wagner

e19043 Background: To describe treatment patterns by lines of systemic (drug) therapy in patients with metastatic melanoma in the U.S. Methods: Using a large U.S. medical claims database, patients were identified between 2005 and 2010 using ≥2 melanoma diagnoses (ICD-9-CM: 172.xx, V10.82) and ≥2 diagnoses for metastasis (ICD-9-CM: 197.xx, 198.xx). Patients were followed from the metastatic diagnosis date to death, disenrollment, or end of study period (6/30/2010), whichever occurred first. Lines of systemic therapy were identified based on the temporal order, gaps, and changes in the drug regimens. Systemic therapies and the duration of therapy in each line were examined. Results: A total of 2,546 patients with metastatic melanoma were included and 985 (38.7%) received systemic therapy. As the first documented therapy after diagnosis, 82.4% of patients received mono-therapy (38.5% temozolomide, 14.3% interleukin-2, 11.4% interferon alfa-2b, 8.2% dacarbazine, 2.9% paclitaxel, 2.5% GM-CSF) and 9.4% received carboplatin plus paclitaxel. Mean duration of mono-therapy was 60 days, ranging from 32 days on interleukin-2 to 124 days on GM-CSF. Of 287 patients (29.1% of previously treated) received subsequent therapy, 68.0% received mono-therapy (26.8% temozolomide, 11.9% interleukin-2, 10.5% dacarbazine, 8.4% paclitaxel, 3.1% interferon alfa-2b, 1.7% GM-CSF), 16.7% carboplatin plus paclitaxel, and 7.3% dacarbazine-containing therapies. Mean duration of mono-therapy was 67 days, ranging from 30 days on interleukin-2 to 238 days on GM-CSF. Among 71 patients who further received additional therapy, mono-therapy was still the dominant regimen (63.4%) with 21.1% temozolomide, 18.3% paclitaxel, 8.5% interleukin-2, 5.6% dacarbazine, 4.2% GM-CSF, and 1.4% interferon alfa-2b. Carboplatin plus paclitaxel was given to 19.7% of patients. Mean duration of mono-therapy was 63 days, ranging from 7 days on interferon alfa-2b to 90 days on temozolomide. Conclusions: The majority of patients with advanced melanoma didn’t receive systemic therapy as captured in the claims database; among those who received systemic therapy, mono-therapy was most common.


2011 ◽  
Vol 21 (3) ◽  
pp. 235-243 ◽  
Author(s):  
Miki Shirakawa Garcia ◽  
Yoko Ono ◽  
Steve R. Martinez ◽  
Steven L. Chen ◽  
Heidi Goodarzi ◽  
...  

2006 ◽  
Vol 175 (1) ◽  
pp. 10-14 ◽  
Author(s):  
G. C. O’Brien ◽  
R. A. Cahill ◽  
D. J. Bouchier-Hayes ◽  
H. P. Redmond

Biotherapy ◽  
1992 ◽  
Vol 4 (4) ◽  
pp. 289-297 ◽  
Author(s):  
Johanna W. Baars ◽  
Johanna C. M. Fonk ◽  
Riekeld J. Scheper ◽  
B. Mary E. von Blomberg-van der Flier ◽  
Herman Bril ◽  
...  

2000 ◽  
Vol 23 (3) ◽  
pp. 387-392 ◽  
Author(s):  
Carlos E. Marroquin ◽  
Donald E. White ◽  
Seth M. Steinberg ◽  
Steven A. Rosenberg ◽  
Douglas J. Schwartzentruber

2007 ◽  
Vol 33 (5) ◽  
pp. 484-496 ◽  
Author(s):  
Teresa Petrella ◽  
Ian Quirt ◽  
Shailendra Verma ◽  
Adam E. Haynes ◽  
Manya Charette ◽  
...  

1991 ◽  
Vol 9 (10) ◽  
pp. 1821-1830 ◽  
Author(s):  
P A Demchak ◽  
J W Mier ◽  
N J Robert ◽  
K O'Brien ◽  
J A Gould ◽  
...  

In this pilot study of metastatic melanoma, interleukin-2 (IL-2) and cisplatin (CDDP) chemotherapy were combined using an alternating schedule designed to explore potential synergism between these modalities. Bolus IL-2 was given at a dose of 600,000 IU/kg intravenously (IV) every 8 hours, days 1 to 5 and 15 to 19, followed by high-dose CDDP administered by two different regimens: (A) 135 to 150 mg/m2 IV bolus over 30 minutes with the chemoprotectant WR-2721 910 mg/m2 or (B) 50 mg/m2 IV over 2 hours every day for 3 days. The trial design allowed an assessment of response to each phase of therapy. Among 27 assessable patients, there were 10 (37%) overall responses, including three (11%) complete responses (CRs) with durations of 9, 16, and 30+ months. Tumor regression was noted in seven patients (partial response [PR], four; minor response [MR], three; response rate [RR], four of 27 [15%]) after IL-2 administration and in 14 patients (PR, 12; MR, two; RR, 12 of 27 [44%]) after CDDP treatment, demonstrating noncrossresistance between the components of the regimen. Major PRs (greater than 90% reduction of tumor burden) or CRs were only seen in patients responding to IL-2. Toxicity during IL-2 therapy was typical for high-dose IL-2 protocols and was reversible. Among the first 20 patients treated with CDDP regimen A, there were eight episodes of grade IV nephrotoxicity (creatinine level greater than 5.0 mg/dL), including three of six patients treated with an initial CDDP dose of 135 mg/m2. This side effect was more frequent among patients with liver metastasis (P less than .05, Fisher's exact test). No significant nephrotoxicity was noted in seven patients treated on regimen B. Although ototoxicity was frequent, minimal bone marrow and neurologic toxicity was noted. There were no treatment-related deaths. This combination showed at least additive activity against melanoma, and the more protracted CDDP schedule was well tolerated. This regimen may serve as a model for future combined immunotherapy and chemotherapy trials in metastatic melanoma.


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