Surgery for Stage IV Metastatic Melanoma

Melanoma ◽  
2018 ◽  
pp. 467-481
Author(s):  
David W. Ollila ◽  
Shachar Laks ◽  
Eddy C. Hsueh
Keyword(s):  
Metastatic Melanoma ◽  
Stage Iv

Adrenalectomy for Metastatic Melanoma: Current Role in the Age of Nonsurgical Treatments

2015 ◽  
Vol 81 (10) ◽  
pp. 1005-1009 ◽  
Author(s):  
Devin C. Flaherty ◽  
Gary B. Deutsch ◽  
Daniel D. Kirchoff ◽  
Jihey Lee ◽  
Kelly T. Huynh ◽  
...  
Keyword(s):  
Overall Survival ◽  
Metastatic Melanoma ◽  
Surgical Resection ◽  
Stage Iv ◽  
Nonoperative Treatment ◽  
Unknown Primary ◽  
Adrenal Metastases ◽  
Term Survival ◽  
Relative Value ◽  
Resection Of Metastases

Surgical resection of metastases to the adrenal gland can improve overall survival of patients with stage IV melanoma, but its relative value with respect to current nonsurgical therapies is unknown. We hypothesized that surgery remains an optimal first-line treatment approach for resectable adrenal metastases. A search of our institution's prospectively collected melanoma database identified stage IV patients treated for adrenal metastases between January 1, 2000, and August 11, 2014. The 91 study patients had a mean age of 60.3 years at diagnosis of adrenal metastasis and 24 had undergone adrenalectomy. Improved survival was associated with an unknown primary lesion, surgical resection, and nonsurgical therapies. Median overall survival from diagnosis of adrenal metastases was 29.2 months with adrenalectomy versus 9.4 months with nonoperative treatment. Adrenalectomy, either as complete metastasectomy or targeted to lesions resistant to systemic therapy, is associated with improved long-term survival in metastatic melanoma.

Sarcoidosis-like syndrome and lymphadenopathy due to checkpoint inhibitors

2016 ◽  
Vol 23 (8) ◽  
pp. 620-624 ◽  
Author(s):  
Belal Firwana ◽  
Rahul Ravilla ◽  
Mihir Raval ◽  
Laura Hutchins ◽  
Fade Mahmoud
Keyword(s):  
Cell Death ◽  
Adverse Event ◽  
T Cell ◽  
Metastatic Melanoma ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Stage Iv ◽  
Stage Iii ◽  
Lymphocyte Antigen

Immunotherapy with checkpoint inhibitors has revolutionized the management of metastatic melanoma. These checkpoints, namely the cytotoxic T lymphocyte antigen 4 and the programmed T cell death 1 receptor, possess an inhibitory effect on the T cell function. Pharmacologic inhibition of cytotoxic T lymphocyte antigen 4 with ipilimumab and programmed T cell death 1 with either pembrolizumab or nivolumab has resulted in long-term sustained responses among patients with metastatic melanoma. The adverse events of these medications are predominantly immune related. Sarcoidosis-like syndrome/lymphadenopathy represents a challenging adverse event to the oncologist as it can be mistaken for progressive disease. Hence, awareness of such adverse event and obtaining a biopsy of the enlarged lymph nodes will confirm the diagnosis and avoid the unnecessary change of current therapies for those with stage IV disease or adding new ones for those with stage III disease. We report three cases of immunotherapy-related sarcoidosis-like syndrome/lymphadenopathy; two cases occurred during adjuvant ipilimumab for stage III surgically resected melanoma and one case during pemprolizumab for stage IV metastatic melanoma.

Prognostic factors in metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9051-9051
Author(s):  
D. R. Minor ◽  
M. Kashani-Sabet ◽  
D. Moore ◽  
C. Kim ◽  
S. S. Venna ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Metastatic Melanoma ◽  
Median Survival ◽  
Performance Status ◽  
Intensive Therapy ◽  
Stage Iv ◽  
Treatment Center ◽  
Term Survival ◽  
Melanoma Patients

9051 Background: Patients with stage IV metastatic melanoma are usually felt to be incurable with a median survival of 6.4 months and a 5-year survival of only 2%. Biochemotherapy has shown promise with long-term survival in selected patients. We felt the study of prognostic factors would determine which patients might benefit the most from this intensive therapy. Methods: 135 consecutive patients with stage IV melanoma treated with decrescendo biochemotherapy followed by maintenance immunotherapy at one melanoma treatment center were studied to determine the most important prognostic factors; these factors were then validated by analysis of 133 patients treated in a multi-center trial at other institutions. Patients were treated using the inpatient regimen of O'Day (JCO23:710s,2005 abstract). Results: Median overall survival (OS) was 16.6 months with 1-year survival of 70% and 5-year survival of 28%. Median progression-free survival (PFS) was 7.6 months with 15% progression-free at 5 years. PFS curves showed no relapses after 30 months, so remissions were durable. For OS performance status 0, normal LDH, stage M1a, and non-visceral sites of metastases were favorable prognostic factors. For PFS performance status 0, normal LDH, female sex, age <50 and stage M1a were favorable prognostic factors Multivariate analysis demonstrated two important prognostic factors for survival: normal serum LDH and the presence of either skin or nodes as one of the sites of metastatic disease. The group with normal LDH and skin or node metastases had a relatively good prognosis with median survival of 44 months and a 5-year survival of 38%. Conversely patients with elevated LDH without any skin or nodal metastases had a poor prognosis, with no long-term survivors. Conclusions: Metastatic melanoma patients treated with biochemotherapy and maintenance immunotherapy that have either a normal LDH or skin or nodes as one of their metastatic sites may have durable remissions of their disease, and this therapy should be studied further in these groups. [Table: see text]

Randomized phase II study of the safety and efficacy of a human anti-αv integrin monoclonal antibody (CNTO 95) alone and in combination with dacarbazine in patients with stage IV metastatic melanoma: 12-month results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9029-9029
Author(s):  
C. Loquai ◽  
A. Pavlick ◽  
D. Lawson ◽  
R. Gutzmer ◽  
J. Richards ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Research And Development ◽  
Metastatic Melanoma ◽  
Single Agent ◽  
Stage Iv ◽  
Progression Free Survival ◽  
Complete Response ◽  
Open Label ◽  
Safety And Efficacy ◽  
To Receive

9029 Objectives: Evaluate the safety and efficacy of CNTO 95, a human anti-αv integrin monoclonal antibody, when administered alone or in combination with dacarbazine (DTIC). Methods: Patients with Stage IV metastatic melanoma were randomized 1:1:1:1 to receive 5 or 10mg/kg CNTO 95 alone, or DTIC (1000mg/m2) + either 10mg/kg CNTO 95 or placebo administered intravenously once every 3 weeks for 8 cycles in the absence of disease progression or unacceptable toxicity. DTIC arms were blinded; single-agent arms were open-label. The primary endpoint was progression free survival (PFS); secondary endpoints included partial response (PR), complete response (CR), stable disease (SD) and overall survival (OS). Major safety endpoints included the incidence of adverse events (AEs) and serious AEs (SAEs). Results: Patients were randomized to receive 5mg/kg CNTO 95 (n=32), 10mg/kg CNTO 95 (n=33), CNTO 95+DTIC (n=32), or placebo+DTIC (n=32). Baseline demographics were similar across groups. The median PFS for CNTO 95+DTIC was 75 days, placebo+DTIC was 54 days and both CNTO 95 alone arms were 42 days. Six patients achieved PR (2–10mg/kg CNTO 95, 1-CNTO 95+DTIC, 3-placebo+DTIC); one patient achieved CR (CNTO 95+DTIC). A higher proportion (43.3%) of patients achieved SD ≥ 12 wks in the CNTO 95+DTIC group compared with the other 3 groups (<20.0%). The median survival was 11.0 months for the patients in the CNTO 95+DTIC arm, 9.8 months and 14.9 months for the 5mg/kg and 10mg/kg arms, and 8.0 months for those in the DTIC control arm. The most common AEs were headache, nausea, fatigue, pyrexia, vomiting and transient uveitic reactions. Three patients (1–5mg/kg, 2-CNTO 95+DTIC) discontinued treatment due to AEs. A higher proportion of patients experienced SAEs in the placebo+DTIC group (29.0%) than in the 5mg/kg (12.9%), 10mg/kg (16.2%) or CNTO 95+DTIC (18.8%) groups. Conclusions: CNTO 95 alone or combined with DTIC was generally well tolerated. In patients with Stage IV metastatic melanoma, a trend toward improvement in PFS, OS and disease control was demonstrated with CNTO 95+DTIC. Centocor, Centocor Research and Development, Inc. Centocor Research and Development, Inc. Johnson & Johnson Centocor Research and Development, Inc. No significant financial relationships to disclose.

A phase II multicenter study on CY-503 in the treatment of patients with unresectable stage IV metastatic melanoma after failure of previous chemotherapy.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. e19015-e19015
Author(s):  
P. Mohr ◽  
U. Trefzer ◽  
R. Gutzmer ◽  
A. Hauschild ◽  
M. Weichenthal ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Phase Ii ◽  
Multicenter Study ◽  
Stage Iv ◽  
Unresectable Stage

Myeloid-derived suppressor cell quantity prior to treatment with ipilimumab at 10mg/kg to predict for overall survival in patients with metastatic melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2518-2518 ◽  
Author(s):  
Shigehisa Kitano ◽  
Michael Andrew Postow ◽  
Czrina Cortez ◽  
Teresa Rasalan ◽  
Humilidad F. Gallardo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Overall Survival ◽  
T Cell ◽  
Metastatic Melanoma ◽  
Peripheral Blood ◽  
Clinical Benefit ◽  
Stage Iv ◽  
T Cell Proliferation ◽  
Pre Treatment

2518 Background: Ipilimumab, an antibody that blocks the function of the immune inhibitory molecule cytotoxic T lymphocyte antigen 4 (CTLA-4), significantly prolongs survival in patients with metastatic melanoma. Approximately 30% of patients derive clinical benefit from therapy. Defining biomarkers of response to ipilimumab therapy would enable selection of patients more likely to respond and is relevant for both practicing clinicians and for clinical trial design. We performed a pilot correlative study evaluating myeloid derived suppressor cells (MDSC), a population of immune suppressive monocytic cells, as a biomarker of clinical outcome. Methods: Peripheral blood from 26 patients with stage IV melanoma treated with ipilimumab 10mg/kg every 3 weeks for 4 doses at our center, as part of an expanded access program (BMS CA184-045) was assessed for MDSC quantity (%CD14+,HLA-DRlow/- cells) pre-treatment, at week 7, week 12, and week 24 by flow cytometry. MDSC ability to inhibit T cell proliferation was tested using an in vitro suppression assay. Results: We found that lower MDSC quantity pre-treatment predicted for improved overall survival (Hazard ratio 1.07 (1.03, 1.11) p=0.002) and trended toward associating with clinical benefit measured at week 24 imaging (p=0.09). This effect was independent of pre-treatment or week 7 absolute lymphocyte counts (ALC) and pre-treatment LDH when evaluated in a multivariate model with ALC and MDSC quantity HR 1.10; 95% CI 1.04, 1.17 p=0.0006 and LDH and MDSC quantity HR 1.06; 95% CI 1.01, 1.11 p = 0.013. Furthermore, a general trend of increasing MDSC number by week 24 from the pre-treatment baseline was associated with patients that did not achieve clinical benefit. MDSC suppressed peripheral blood T cell proliferation as measured by CFSE dilution in response to anti-CD3 antibody stimulation. Conclusions: Pre-treatment MDSC quantity may predict clinical response following ipilimumab therapy. Further studies evaluating MDSC as a biomarker of ipilimumab therapy are warranted both retrospectively and prospectively in a broader group of patients.

A phase I/II study to evaluate the ability of decitabine and panobinostat to improve temozolomide chemosensitivity in metastatic melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3056-3056
Author(s):  
Chang Xia ◽  
Douglas Earl Laux ◽  
Jeremy Michael Deutsch ◽  
Melanie Frees ◽  
Brian Smith ◽  
...  
Keyword(s):  
Phase I ◽  
Metastatic Melanoma ◽  
Performance Status ◽  
Safety Data ◽  
Stage Iv ◽  
Median Number ◽  
Maximum Tolerated Dose ◽  
Primary Endpoints ◽  
Number Of Cycles ◽  
Ecog Ps

3056 Background: Epigenetic gene regulation is likely a contributing mechanism of cancer initiation and progression. Emerging evidence indicates that epigenetics may also play a key role in the development of chemoresistance in melanoma. We proposed combining the histone deacetylase inhibitor panobinostat (PT) and the demethylator decitabine (D) to overcome the development of epigenetic mediated temozolomide (TMZ) resistance in metastatic melanoma. Methods: Eligible patients must be ≥18, stage IV melanoma, and naïve or previously treated, with good performance status (ECOG ≤ 2) and normal organ functions. Patients with previous exposure to TMZ were allowed on study. The study includes the dose escalation of D and PT followed by expansion cohorts. D (0.1mg/kg SQ, 0.2mg/kg SQ) on days 1, 3, 5, 8, 10,12, PT (10mg PO, 20mg PO, 30mg PO) Q96h starting day 8, and TMZ 150mg/m2 PO daily on days 9-13 of each 42 day cycle. TMZ was increased to 200mg/m2 in the absence of grade 2 thrombocytopenia. Primary endpoints of phase I study are to determine the toxicity, safety and maximum tolerated dose (MTD) of the D, PT and TMZ combination. Results: To date, the phase I portion of this trial is completed. We report on the safety data for this combination. 17 patients received treatment (1st cohort: 5; 2nd cohort: 4; 3rd cohort: 4; 4th cohort: 4 ). M:F 11:6. Median age: 56 (32-77); Median ECOG PS: 1; 82% of the patients received at least one cycle (n=14). Median number of cycles given: 2 (0-6). To date, no DLTs have occurred. The MTD was not reached. The only grade (G) 4 adverse event (AE) is neutropenia on a patient in cohort 3 and it resolved within 3 days. G3 AEs included lymphopenia (n=4, 23%), anemia (n=2, 12%), leukopenia (n=2, 12%) and fatigue (n=2, 12%). Common G2 toxicities were leukopenia (n=5, 30%), neutropenia (n=4, 23%), nausea (n=4, 23%) and lymphopenia (n=3, 18%). Conclusions: The combination of D, PT, and TMZ appears to be safe and well-tolerated. The recommended dose for the phase II study remains to be determined.

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