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Successful control of heavily pretreated metastatic gastric cancer with the mTOR inhibitor everolimus (RAD001) in a patient with PIK3CA mutation and pS6 overexpression.

Park JH, Ryu MH, Park YS, Park SR, Na YS, Rhoo BY, Kang YK - BMC Cancer (2015)

Bottom Line: Everolimus was re-tried as salvage chemotherapy (re-treatment), and the patient achieved stable disease for 1 year until his death.After two cycles of everolimus re-treatment, the overexpression of pS6 became nearly absent in follow-up IHC staining.Everolimus monotherapy was satisfactory in a patient with refractory metastatic GC harboring PIK3CA and pS6 aberrations.

View Article: PubMed Central - PubMed

Affiliation: Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea. irvineusa@hanmail.net.

ABSTRACT

Background: Everolimus (RAD001) is an orally administered mTOR inhibitor that is well known for its antitumor efficacy and that has been approved for the treatment of several solid tumors, including renal cell carcinoma. In gastric cancer (GC), despite previous preclinical and phase I/II studies suggesting the promising efficacy of everolimus in previously treated AGC, more recent trials revealed that only certain subsets of patients might benefit from treatment with everolimus.

Case presentation: A 26-year-old man with metastatic gastric cancer with multiple liver lesions was treated with everolimus after failure of 1st-line and 2nd-line chemotherapy. A durable partial response was achieved for over 2 years. After progression from initial everolimus treatment, sequential cytotoxic chemotherapies were tried but failed rapidly. Everolimus was re-tried as salvage chemotherapy (re-treatment), and the patient achieved stable disease for 1 year until his death. Subsequent mutational analysis and immunohistochemical (IHC) staining with the tumor tissues just before re-treatment with everolimus revealed a PIK3CA hotspot mutation and pS6 overexpression in the primary tumor. After two cycles of everolimus re-treatment, the overexpression of pS6 became nearly absent in follow-up IHC staining.

Conclusions: Everolimus monotherapy was satisfactory in a patient with refractory metastatic GC harboring PIK3CA and pS6 aberrations. These molecular alterations might be potential biomarkers that can predict the treatment response of everolimus, particularly in the terms of durable disease control. This case suggests and emphasizes that close evaluation of biomarkers in tumor tissue may be essential for identifying highly favorable groups among various subpopulations with AGC.

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Related in: MedlinePlus

The patient received initial treatment of everolimus 10 mg/d as the third-line chemotherapy. CT scans were taken every 2 months during the initial treatment period. CT scans reveal the diffuse liver metastases before treatment with everolimus (A). After 1 year and 2 months of everolimus 10 mg/d, partial response was achieved (B).
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Fig1: The patient received initial treatment of everolimus 10 mg/d as the third-line chemotherapy. CT scans were taken every 2 months during the initial treatment period. CT scans reveal the diffuse liver metastases before treatment with everolimus (A). After 1 year and 2 months of everolimus 10 mg/d, partial response was achieved (B).

Mentions: A 26-year-old Korean male was diagnosed with stage IV poorly differentiated gastric adenocarcinoma of the lower body with multiple liver metastases in August 2009. The initial diagnosis was made at an outside hospital using abdominopelvic computed-tomography (CT) and endoscopic biopsy of stomach. The pathologic specimen at the time of diagnosis was not procured. The patient was initially treated with systemic chemotherapies, including three cycles of S-1 and subsequently four cycles of FOLFOX chemotherapy, resulting in the progression of liver metastasis. After second-line chemotherapy, the patient was transferred to our institute (Asan medical center, Seoul, Korea) for further management in September 2008. Baseline tumor tissue was obtained via endoscopic forceps biopsy before treatment. As third-line chemotherapy, the patient was enrolled in an open-labeled, phase II trial evaluating the efficacy of everolimus 10 mg/day, and he achieved a partial response by the Response Evaluation Criteria in Solid Tumors (RECIST) as the best response after 1 year and 2 months (Figure 1A and B). The tumor remained stable with a partial response over 2 years in this initial treatment of everolimus. However, after 29 months of initial everolimus treatment, abdominopelvic CT revealed the progression of liver metastasis. An episodic pneumonia due to streptococcus occurred right after disease evaluation, and the patient underwent antibiotic treatment for a month. Subsequently, the patient underwent salvage chemotherapy with FOLFIRI but failed after 3 cycles with disease progression. Sequential three cycles of oral paclitaxel and six cycles of docetaxel chemotherapy were applied to the patient for 4 months to maintain stable disease. During the period of docetaxel treatment, however, the patient suffered from general weakness accompanied by poor compliance and eventually failed the treatment. In such circumstances, we decided to resume the everolimus monotherapy as salvage chemotherapy.Figure 1


Successful control of heavily pretreated metastatic gastric cancer with the mTOR inhibitor everolimus (RAD001) in a patient with PIK3CA mutation and pS6 overexpression.

Park JH, Ryu MH, Park YS, Park SR, Na YS, Rhoo BY, Kang YK - BMC Cancer (2015)

The patient received initial treatment of everolimus 10 mg/d as the third-line chemotherapy. CT scans were taken every 2 months during the initial treatment period. CT scans reveal the diffuse liver metastases before treatment with everolimus (A). After 1 year and 2 months of everolimus 10 mg/d, partial response was achieved (B).
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4374284&req=5

Fig1: The patient received initial treatment of everolimus 10 mg/d as the third-line chemotherapy. CT scans were taken every 2 months during the initial treatment period. CT scans reveal the diffuse liver metastases before treatment with everolimus (A). After 1 year and 2 months of everolimus 10 mg/d, partial response was achieved (B).
Mentions: A 26-year-old Korean male was diagnosed with stage IV poorly differentiated gastric adenocarcinoma of the lower body with multiple liver metastases in August 2009. The initial diagnosis was made at an outside hospital using abdominopelvic computed-tomography (CT) and endoscopic biopsy of stomach. The pathologic specimen at the time of diagnosis was not procured. The patient was initially treated with systemic chemotherapies, including three cycles of S-1 and subsequently four cycles of FOLFOX chemotherapy, resulting in the progression of liver metastasis. After second-line chemotherapy, the patient was transferred to our institute (Asan medical center, Seoul, Korea) for further management in September 2008. Baseline tumor tissue was obtained via endoscopic forceps biopsy before treatment. As third-line chemotherapy, the patient was enrolled in an open-labeled, phase II trial evaluating the efficacy of everolimus 10 mg/day, and he achieved a partial response by the Response Evaluation Criteria in Solid Tumors (RECIST) as the best response after 1 year and 2 months (Figure 1A and B). The tumor remained stable with a partial response over 2 years in this initial treatment of everolimus. However, after 29 months of initial everolimus treatment, abdominopelvic CT revealed the progression of liver metastasis. An episodic pneumonia due to streptococcus occurred right after disease evaluation, and the patient underwent antibiotic treatment for a month. Subsequently, the patient underwent salvage chemotherapy with FOLFIRI but failed after 3 cycles with disease progression. Sequential three cycles of oral paclitaxel and six cycles of docetaxel chemotherapy were applied to the patient for 4 months to maintain stable disease. During the period of docetaxel treatment, however, the patient suffered from general weakness accompanied by poor compliance and eventually failed the treatment. In such circumstances, we decided to resume the everolimus monotherapy as salvage chemotherapy.Figure 1

Bottom Line: Everolimus was re-tried as salvage chemotherapy (re-treatment), and the patient achieved stable disease for 1 year until his death.After two cycles of everolimus re-treatment, the overexpression of pS6 became nearly absent in follow-up IHC staining.Everolimus monotherapy was satisfactory in a patient with refractory metastatic GC harboring PIK3CA and pS6 aberrations.

View Article: PubMed Central - PubMed

Affiliation: Departments of Oncology, Asan Medical Center, University of Ulsan College of Medicine, 88 Olympic-ro 43-gil, Songpa-gu, Seoul, 138-736, South Korea. irvineusa@hanmail.net.

ABSTRACT

Background: Everolimus (RAD001) is an orally administered mTOR inhibitor that is well known for its antitumor efficacy and that has been approved for the treatment of several solid tumors, including renal cell carcinoma. In gastric cancer (GC), despite previous preclinical and phase I/II studies suggesting the promising efficacy of everolimus in previously treated AGC, more recent trials revealed that only certain subsets of patients might benefit from treatment with everolimus.

Case presentation: A 26-year-old man with metastatic gastric cancer with multiple liver lesions was treated with everolimus after failure of 1st-line and 2nd-line chemotherapy. A durable partial response was achieved for over 2 years. After progression from initial everolimus treatment, sequential cytotoxic chemotherapies were tried but failed rapidly. Everolimus was re-tried as salvage chemotherapy (re-treatment), and the patient achieved stable disease for 1 year until his death. Subsequent mutational analysis and immunohistochemical (IHC) staining with the tumor tissues just before re-treatment with everolimus revealed a PIK3CA hotspot mutation and pS6 overexpression in the primary tumor. After two cycles of everolimus re-treatment, the overexpression of pS6 became nearly absent in follow-up IHC staining.

Conclusions: Everolimus monotherapy was satisfactory in a patient with refractory metastatic GC harboring PIK3CA and pS6 aberrations. These molecular alterations might be potential biomarkers that can predict the treatment response of everolimus, particularly in the terms of durable disease control. This case suggests and emphasizes that close evaluation of biomarkers in tumor tissue may be essential for identifying highly favorable groups among various subpopulations with AGC.

Show MeSH
Related in: MedlinePlus