Complete response in a melanoma patient treated with imatinib

2012 ◽  
Vol 126 (6) ◽  
pp. 638-640 ◽  
Author(s):  
M C Brown ◽  
R J Casasola

AbstractBackground:Imatinib therapy has been successful in gastrointestinal stromal tumours containing mutation of the KIT gene. However, there are few reported cases of successful imatinib therapy in patients with melanoma containing KIT gene mutation or c-kit protein expression.Methods and results:A 52-year-old man developed metastatic melanoma from a primary melanoma in the left side of the nasopharynx. The tumour was positive for c-kit protein, and there was a KIT mutation in exon 11. He was treated with imatinib. A follow-up scan one year later showed a complete response. Treatment targeting the biological characteristics of melanoma proved successful in this patient.

Sarcoma ◽  
1998 ◽  
Vol 2 (3-4) ◽  
pp. 171-177
Author(s):  
S. Murray Yule ◽  
Roderick Skinner ◽  
Martin W. English ◽  
Mike Cole ◽  
Andrew D. J. Pearson ◽  
...  

Background.Although the survival of children with soft tissue sarcoma (STS) has improved considerably, the outcome of patients with metastatic disease, and those with primary tumours of the extremities or parameningeal sites remains disappointing. We describe the clinical outcome of an ifosfamide-based regimen with local therapy directed only to children who failed to achieve a complete response to initial chemotherapy.Patients and Methods.Twenty-one children with STS (16 rhabdomyosarcoma) who presented with unresectable tumours were treated with five courses of ifosfamide (9 g/m2) and etoposide (600 mg/m2). Patients who did not achieve a complete response then received local therapy. Chemotherapy with ifosfamide combined with etoposide, vincristine (1.5 mg/m2and doxorubicin (60 mg/m2) or vincristine and actinomycin D (1.5 mg/m2) was continued for one year.Results and Discussion.Objective responses to five courses of ifosfamide and etoposide were seen in all patients. Disease free survival (DFS) at a median follow up of 59 months was 57% (95% CI 29–75%). The DFS of children who received local therapy was 89% compared with 33% in those who received chemotherapy alone (p=0.027). Locoregional recurrences did not occur in children who received radiotherapy to the site of the primary tumour. Ifosfamide-based chemotherapy does not reduce the incidence of loco-regional recurrence in children who do not receive local therapy.


Blood ◽  
2008 ◽  
Vol 112 (5) ◽  
pp. 1655-1657 ◽  
Author(s):  
Karl M. Hoffmann ◽  
Andrea Moser ◽  
Peter Lohse ◽  
Andreas Winkler ◽  
Barbara Binder ◽  
...  

Abstract Cutaneous mastocytosis (CM) in children is a usually benign skin disorder caused by mast cell proliferation. Progressive disease leading to systemic involvement and fatal outcomes has been described. C-kit receptor mutations have been identified as causative for CM, some of which potentially respond to imatinib treatment as described for patients with systemic mastocytosis. We report successful therapy of progressive CM with imatinib in a 23-month-old boy. KIT gene analysis revealed not only a somatic deletion of codon 419 in exon 8 (c.1255_1257delGAC) which responds to imatinib therapy, but also a novel germ line p. Ser840Asn substitution encoded by exon 18 in the c-kit kinase domain. Family history suggests this exchange does not affect receptor function or cause disease. Imatinib therapy was well tolerated, stopped symptoms and disease progression, and appeared to shorten the course of the disease. Imatinib could possibly represent a novel therapeutic option in patients with progressive CM.


Author(s):  
M. Bharathidasan ◽  
B. Justin William ◽  
Ravi Sundar George Sundar George ◽  
A. Arunprasad ◽  
R. Sivasankar

A two years old Kathiawar stallion was reported with the history of two, pedunculated hard mass medially on the thigh and hock of the right hind limb, progressively increasing for the past two months. Fine needle aspiration cytology revealed fibrosarcoma.The tumour on the medial aspect of the thigh was injected with cisplatin intra-tumorally at a dose rate of 0.3 mg/cm3 of tumour volume and was exposed to ECT. The tumour on the medial aspect of the hock was excised incompletely to preserve skin and subcutaneous tissues around the tumour for wound opposition and treated with intra-tumoral injection of cisplatin followed by ECT. Following electrochemotherapy complete response was noticed onthe 3rd and 4th week for the tumours on the thigh and hock respectively. No recurrence was noticed during the follow-up period of one year revealing ETC with cisplatin as a single treatment and also in combination with surgery is effective for the treatment of fibrosarcoma in equines.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 9528-9528 ◽  
Author(s):  
C. D. Blanke ◽  
G. D. Demetri ◽  
M. Von Mehren ◽  
M. C. Heinrich ◽  
B. L. Eisenberg ◽  
...  

9528 Background: Imatinib achieves tumor control in most pts with advanced GIST, but the durability of remissions has not been well described. We now present an updated long-term analysis of a randomized phase II trial first presented in 2001, with a median follow-up of 52 months. Methods: 147 pts with unresectable or metastatic malignant GIST were randomized to treatment with daily dosing of imatinib, 400 or 600 mg po. Results: Two pts (1%) achieved a complete response, 98 (67%) achieved a partial response (PR), and 23 (16%) exhibited stable disease (SD) as their best response. Median time-to-response was 13 weeks (95% CI; 12–23 weeks), but one quarter of pts responded after 23 weeks. No significant response differences were seen between the two dose levels tested. The median duration of response was 27 months, and median overall survival was 58 months. Pts with SD or PR had similar 4-year survival rates (64% versus 62%). KIT and/or PDGFRA mutational analyses were obtained in 87% of patients, and the mutational status was highly significant in predicting outcome. GISTs harboring KIT mutations in exon 11, exon 9, and with no detectable mutations in KIT or PDGFRA demonstrated PR rates of 87%, 48%, and 0%, respectively. The median survival for pts with exon 11 KIT mutations has not yet been reached, and it was 45 months for those with exon 9 mutations. Conclusions: While late progression can be seen in GIST pts treated with imatinib, the majority of pts derive benefit. Survival in those achieving SD parallels those with PRs. Late responses are often seen in pts with initial SD, and responses in general are of lasting duration. In particular, pts with KIT mutations in exon 11 (the most common exon affected) have very high response rates and favorable long term survival. [Table: see text]


2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 199-199
Author(s):  
Meredith Ann McKean ◽  
Junna Oba ◽  
Junsheng Ma ◽  
Lauren Elaine Haydu ◽  
Roland L. Bassett ◽  
...  

199 Background: KIT-mutated MM is a rare melanoma entity. Response rates of KIT-mutated MM to anti CTLA-4 and anti PD-1 have not previously been reported. Methods: A single-institution retrospective review identified patients (pts) with KIT-mutated MM treated with at least two doses of anti CTLA-4 or anti PD-1 between 2008-2017 with response determined by immune-related response criteria (irRC). Overall survival (OS) was from ICI start to death or last follow-up date, and progression-free-survival (PFS) was from ICI start to date of progression or death if pts deceased without disease progression. Results: Thirty-five pts treated with ipilimumab were identified. Median follow-up was 63.7 months. Median age at MM diagnosis was 65.4 years (range 26-81) and 54.3% were male. Subtypes were 51.4% mucosal, 22.9% acral-lentiginous, 22.9% cutaneous, and 2.9% unknown primary. KIT mutations were 57.1% exon 11, 25.7% exon 17, 11.4% exon 13, and 5.7% exon 2. Anatomical M stage at treatment initiation was 11.4% M1a, 34.3% M1b, and 54.3% M1c. Median OS was 11.8 months (8.4-35.6) and PFS was 3.0 months (2.8-5.8). Responses to ipilimumab were 8.6% complete response (CR), 11.4% partial response (PR), 28.6% stable disease (SD), and 51.4% progressive disease (PD) for a 48.6% clinical response rate (CRR). Twenty pts treated with anti PD-1 were identified. Median follow-up was 7.9 months. Median age at MM diagnosis was 66.7 years (range 42.6-86.8) and 70% were male. Subtypes were 40% mucosal, 30% cutaneous, 20% acral-lentiginous, and 10% unknown primary. KIT mutations were 45% exon 11, 35% exon 17, 10% exon 2, 5% exon 13 and and 5% exon 10. Anatomical M stage at treatment initiation was 10% M1a, 15% M1b, and 75% M1c. Median OS was 22.5 months (7.4-NA ) and PFS was 3.2 months (2.7-NA). Responses to anti PD-1 were 10.0% CR, 25.0% PR, 20.0% SD, and 45.0% PD for a 55.0% CRR. For both anti CTLA-4 and anti PD-1 treated cohorts, univariate analysis demonstrated no statistical significance between tumor response to ICI and clinical pt characteristics or KIT mutation exon. Conclusions: KIT-mutated MM demonstrated CRR of 48.6-55.0% to ICI. There was no correlation between pt characteristics or KIT exon mutation and response to therapy; however, analysis was limited by sample size.


2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 181-181 ◽  
Author(s):  
Ahmad A. Tarhini ◽  
Yan Lin ◽  
Joseph J. Drabick ◽  
Rogerio Izar Neves ◽  
Marc S. Ernstoff ◽  
...  

181 Background: Neoadjuvant pembrolizumab at 200 mg in combination with high dose IFNα2b (HDI) for locally/regionally advanced or recurrent melanoma may improve the clinical outcomes of these high risk patients (pts), and provide access to blood and tumor pre/post pembro-HDI to illuminate the host effector and suppressor immune mechanisms. Methods: Pts were treated with pembro 200 mg IV every 3 weeks (wk) x 2 doses followed by definitive surgery, then every 3 wks for up to one year. HDI (20 MU/m²/d IV x 5 days (d)/wk for 4 wks then 10 MU/m²/d SC every other d TIW for 48 wks) was given concurrently. Tumor samples were obtained at baseline and at definitive surgery (wk 6-8) and serum/PBMC at baseline, 6 wks, 3, 6, 12 months (mo). Results: Twenty evaluable pts (14 male, 6 female, 14 cutaneous primary, 4 unknown, 3 mucosal), age 29-82 were treated. 5 had Stage IIIB (N1b, N2b, M2c), 11 IIIC (N3) and 4 IV (M1a, M1b) melanoma. Over 230 cycles have been delivered to date (median 14). Worst toxicities included grade (Gr) 3: fatigue (8; 40%), ↑CPK (5; 25%), hypophosphatemia (5; 25%), ↑lipase (3; 15%), lymphopenia (3; 15%), hypertension (2; 10%), diarrhea/colitis (1; 5%), arthralgia (1, 5%), syncope (1, 5%), hyponatremia (1, 5%), neutropenia (1; 5%), anemia (1, 5.00%) nausea (2, 10%), flu like symptoms (1, 5%). There were 3 Gr 4 events (CPK, hyperglycemia, lymphopenia). One suspected grade 5 event occurred 6 months after completion of therapy with autopsy evidence of pneumonia and myocarditis. Among 20 evaluable pts, 4 relapsed and 1 died. Median follow-up for pts who have not relapsed is 11 months. The radiologic preoperative response rate (WHO; unconfirmed) was 65%. The pathologic complete response rate (no viable tumor on histologic assessment) was 35%. Conclusions: Neoadjuvant pembro-HDI exhibited promising clinical activity. Longer follow up is underway in order to define the long term benefits and risks. Clinical trial information: NCT02339324.


2017 ◽  
Vol 06 (03) ◽  
pp. 113-117 ◽  
Author(s):  
Trupti Pai ◽  
Munita Bal ◽  
Omshree Shetty ◽  
Mamta Gurav ◽  
Vikas Ostwal ◽  
...  

Abstract Background: Primary mutations in the KIT gene are the driving force for gastrointestinal stromal tumors (GIST) tumorigenesis. Predictive role of KIT mutation status aids oncologists in patient management. There is a paucity of comprehensive data on the frequency of mutations in the KIT gene in GIST affecting Indian patients. The aims of this study were to determine the frequency and spectrum of molecular alterations affecting the KIT gene and assess their association with clinicopathologic features in a cohort of patients of GIST. Materials and Methods: Morphological and immunohistochemically confirmed GIST cases (n = 114) accessioned from August 2014-June 2015 were analyzed for mutations in KIT exons 9, 11, 13, and 17 and subjected to Sanger sequencing onto the ABI 3500 Genetic Analyzer. The sequences were analyzed using sequence analysis software: SeqScape® and Chromas Lite. Results: KIT mutations were seen in 70% of cases and the majority of KIT mutations involved exon 11 (57%), followed by exon 9 (10%), exon 13 (3%), and exon 17 (1%). Most common exon 11 mutations were in-frame deletions (61.4%) followed by substitution mutations (19.3%). Exon 9 mutations showed identical duplication of Ala-Tyr at codons 502–503. Simultaneous mutations affecting exon 11 and 13 were discovered. Novel variations, namely, p.Q556E (c.1666C>G), p.Q556dup (c.1666_1668dupCAG), p.K558_V559delinsS (c.1672_1677delAAGGTTinsAGT), p.Y503_F504insTY (c.1509_1510insACCTAT), and p.K642R (c.1925A>G) involving exons 11, 9, and 13, respectively, were observed. Interpretation and Conclusions: First study with complete analysis of all 4 exons of KIT (exons 9, 11, 13, and 17) in Indian GIST patients. Along with well-described KIT mutations, several rare double mutations as well as novel alterations were reported in this series.


1994 ◽  
Vol 5 (3) ◽  
pp. 182-185 ◽  
Author(s):  
L Olmos ◽  
J Vilata ◽  
A Rodríguez Pichardo ◽  
A Lloret ◽  
A Ojeda ◽  
...  

A randomized, double-blind, placebo-controlled trial was conducted to assess interferon-beta efficacy and safety in the treatment of anogenital condylomatous lesions. One hundred patients received a daily intramuscular injection of either interferon-beta (IFN-β) (2 MIU/day) or placebo for 10 days. Of 94 evaluable patients, the complete response rate observed 8 weeks after treatment was significantly higher in the group receiving IFN-β, as compared to the placebo-treated group (51% vs 28.9%, P<0.05). After one year, 24 patients (100%) out of 24 complete responders to IFN-β who attended for follow-up remained free of lesions. Twelve of 13 patients with complete response to placebo (92.3%) remained free of lesions after one year. Side effects were mild and no significant analytical changes were observed. In conclusion, interferon-beta is an effective and safe treatment for long-term eradication of anogenital condylomatous lesions.


Author(s):  
Devendra Parmar ◽  
Kinnari Thacker ◽  
Jay Shah

<p class="abstract"><strong>Background:</strong> <span lang="EN-IN">Oral lichen planus (OLP) is a common mucocutaneous disorder that affects 1-2% of the adult general population and slight predominance in females has been observed. The success rate is not satisfactory with these modalities of treatment, so there is a clear need for alternative therapy. This study was done to evaluate the efficacy of griseofulvin in the treatment of lichen planus.</span></p><p class="abstract"><strong>Methods:</strong> <span lang="EN-IN">The present study was conducted in the department of dermatology in the medical institution for the period of one year. The study included the initial assessment of 60 patients who were diagnosed with lichen planus (LP). Patients with both sexes and age between 15-60 years who agreed to come on follow up examination were included. All patients were treated with griseofulvin 500 mg/day for 6 months. Response of treatment was assessed by clinical examination at each subsequent visit (every two weeks)</span>.<strong></strong></p><p class="abstract"><strong>Results:</strong> <span lang="EN-IN">Among patients with OLP, there was complete response in 27%, moderate improvement in 51%, and no response in 22% of cases. Complete clinical response of cutaneous LP was seen in 18% cases, no response was found in same number of patient, 64% no. of cases showed moderate response. </span></p><p class="abstract"><strong>Conclusions:</strong> <span lang="EN-IN">Griseofulvin gives complete improvement in 27% cases and moderate improvement in 51% cases in OLP and it gives complete improvement in 16% cases in cutaneous LP after treatment of 6 months. This study was done on a small scale and without any control group, so conclusive comments could not be passed.</span></p>


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