Effective Use of Thalidomide in the Treatment of Recurrent Metastatic Chordoma

Chay, Wen Yee; Sittampalam, Kesavan; Toh, Han Chong

doi:10.1200/jco.2010.34.2139

Cited by 14 publications

(14 citation statements)

References 16 publications

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“…One of 15 patients (7%) had an objective radiographic response, and the median PFS was 9.9 months [ 43 ]. Thalidomide has also been reported to induce a radiographic response in one case report [ 44 ]. Despite intermittent reports of activity with various agents, there is no clear standard of treatment in the advanced disease setting.…”

Section: Systemic Treatmentmentioning

confidence: 99%

Chordoma: The Quest for Better Treatment Options

Heery

2016

Oncol Ther

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Chordoma is an extremely rare cancer, with an incidence of about one case per million persons per year in the USA and Europe (about 300 and 450 cases per year, respectively). The estimated median overall survival of patients with chordoma is approximately 6–7 years, yielding a rough estimate of chordoma prevalence at about 2000 in the USA and 3000 in Europe. Primary tumor develops along the axial spine between the clivus and sacrum and develops from the residual embryonic notochord. Brachyury (T), a transcription factor required for normal embryonic development, is expressed in the notochord and overexpressed in almost all cases of chordoma. The primary treatment for chordoma is surgical excision with wide local margins, when possible. Radiotherapy also plays a significant role in the adjuvant setting and when surgery is not possible. Unfortunately, in the advanced and/or metastatic setting, where the role of surgery and/or radiation is less clear, treatment options are very limited. To date, there have been no randomized, controlled trials in chordoma that have resulted in defined agents of clinical benefit for systemic treatment. This review briefly describes the natural history and initial treatment of chordoma and focuses on treatment options for advanced disease and potential avenues of research that may lead to improved treatment options in the future.

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Section: Systemic Treatmentmentioning

confidence: 99%

Chordoma: The Quest for Better Treatment Options

Heery

2016

Oncol Ther

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“…Imatinib was assessed in 18 studies with a total of 221 patients (10, 16, 17, 19, 23–28, 32, 34–36, 38, 39, 41, 42), erlotinib in 10 studies with 16 patients (13, 17, 22, 33, 35, 38, 40–42), cetuximab in five studies (seven patients) (13, 30, 31, 33, 41), sorafenib in four studies (65 patients) (15, 17, 21, 37), pazopanib in four studies with seven patients (16, 28, 41, 43) and sunitinib in three studies with 11 patients (14, 17, 28). Sirolimus, thalidomide, bevacizumab, gefitinib, linsitinib, and everolimus were accessed in two studies each (13, 22, 25, 28–31, 33, 34, 40–42), whereas dasatinib (32 patients) (11), lapatinib (18 patients) (12), rapamycin (one patients) (34), temosirolimus (one patients) (17) and yeast-brachyury (GI-6301) vaccine (11 patients) (20) were only analyzed in one study each (Figures 2 and 3). Monotherapy of MTTs was reported in 24 studies (10–12, 14–17, 20, 21, 23, 24, 26–28, 32, 34–39, 41, 43, 44) with combination therapy in 13 studies (13, 19, 22, 25, 28–31, 33, 39–42).…”

Section: Resultsmentioning

confidence: 99%

“…Sirolimus, thalidomide, bevacizumab, gefitinib, linsitinib, and everolimus were accessed in two studies each (13, 22, 25, 28–31, 33, 34, 40–42), whereas dasatinib (32 patients) (11), lapatinib (18 patients) (12), rapamycin (one patients) (34), temosirolimus (one patients) (17) and yeast-brachyury (GI-6301) vaccine (11 patients) (20) were only analyzed in one study each (Figures 2 and 3). Monotherapy of MTTs was reported in 24 studies (10–12, 14–17, 20, 21, 23, 24, 26–28, 32, 34–39, 41, 43, 44) with combination therapy in 13 studies (13, 19, 22, 25, 28–31, 33, 39–42).…”

Section: Resultsmentioning

confidence: 99%

“…Eighteen studies investigated the therapeutic efficacy of IM on 221 patients (10, 16, 17, 19, 23–28, 32, 34–36, 38, 39, 41, 42), including three clinical trials (10, 19, 28), seven retrospective case series (16, 17, 23–27), and eight case reports (32, 34–36, 38, 39, 41, 42). Fourteen studies (204 patients) analyzed the efficacy of imatinib as monotherapy (10, 16, 17, 23, 24, 26–28, 32, 34–36, 39, 41), of which four studies (181 patients) used RECIST and 3 were focused on PDGFRβ-expressing chordoma. In these four studies, four patients achieved partial response (PR) (2.2%), 133 cases sustained stable disease (SD) (73.5%) and 44 cases experienced progressive disease (PD) (24.3%) (10, 17, 26, 27, 32).…”

Section: Resultsmentioning

confidence: 99%

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Molecular Targeted Therapy in the Treatment of Chordoma: A Systematic Review

et al. 2019

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Objectives: Chordoma is a rare bone malignancy that affects the spine and skull base. Treatment dilemma leads to a high rate of local relapse and distant metastases. Molecular targeted therapy (MTT) is an option for advanced chordoma, but its therapeutic efficacy and safety have not been investigated systematically. Therefore, a systematic review was conducted on studies reporting MTT regimens for chordoma.Methods: Clinical trials, case series and case reports on chordoma MTT were identified using MEDLINE, Cochrane library and EMBASE, and systematically reviewed. Data on clinical outcomes, such as median overall survival, progression-free survival, response rate and adverse events (AEs) were extracted and analyzed.Results: Thirty-three eligible studies were selected for the systematic review, which indicated that imatinib and erlotinib were the most frequently used molecular targeted inhibitors (MTIs) for chordoma. For PDGFR-positive and/or EGFR-positive chordoma, clinical benefits were achieved with acceptable AEs. Monotherapy is preferred as the first-line of treatment, and combined drug therapy as the second-line treatment. In addition, the brachyury vaccine has shown promising results.Conclusions: The selection of MTIs for patients with advanced or relapsed chordoma should be based on gene mutation screening and immunohistochemistry (IHC). Monotherapy of TKIs is recommended as the first-line management, and combination therapy (two TKIs or TKI plus mTOR inhibitor) may be the choice for drug-resistant chordoma. Brachyury vaccine is a promising therapeutic strategy and requires more clinical trials to evaluate its safety and efficacy.

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“…Few clinical trials investigating PI3K/AKT/mTOR inhibition in chordomas exist to date; current trials implement mTOR inhibitors secondary to other small-molecule inhibitors ( 43 ). A small number of published case reports found neither rapamycin or everolimus monotherapy to be efficacious ( 34 , 67 ), despite prior suggestion of rapamycin-responsiveness in patient-derived cell lines ( 68 ). A randomized investigation of these therapies may further clarify their efficacy in chordoma treatment.…”

Section: Growth Factor Signalingmentioning

confidence: 99%

Translational Windows in Chordoma: A Target Appraisal

et al. 2020

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Chordomas are rare tumors that are notoriously refractory to chemotherapy and radiotherapy when radical surgical resection is not achieved or upon recurrence after maximally aggressive treatment. The study of chordomas has been complicated by small patient cohorts and few available model systems due to the rarity of these tumors. Emerging next-generation sequencing technologies have broadened understanding of this disease by implicating novel pathways for possible targeted therapy. Mutations in cell-cycle regulation and chromatin remodeling genes have been identified in chordomas, but their significance remains unknown. Investigation of the immune microenvironment of these tumors suggests that checkpoint protein expression may influence prognosis, and adjuvant immunotherapy may improve patient outcome. Finally, growing evidence supports aberrant growth factor signaling as potential pathogenic mechanisms in chordoma. In this review, we characterize the impact on treatment opportunities offered by the genomic and immunologic landscape of this tumor.

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Effective Use of Thalidomide in the Treatment of Recurrent Metastatic Chordoma

Cited by 14 publications

References 16 publications

Chordoma: The Quest for Better Treatment Options

Chordoma: The Quest for Better Treatment Options

Molecular Targeted Therapy in the Treatment of Chordoma: A Systematic Review

Translational Windows in Chordoma: A Target Appraisal

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