Arekapudi S

Background: Capecitabine is an oral precursor of 5-FU (5' deoxy-5-fluoridine), a commonly prescribed chemotherapeutic agent to treat gastrointestinal and breast cancers. Capecitabine is currently contraindicated in patients with severe renal failure with Glomerular filtration rate <
30 ml/min. Literature review shows limited evidence in safety and effectiveness of using capecitabine in patients undergoing hemodialysis.

Case Report 1: A 75-year-old old male with a history of end stage renal disease on hemodialysis, was diagnosed with a 10 cm duodenal mass on CT scan when presented with three months history of abdominal pain and 45 lb weight loss. esophagogastroduodenoscopy and biopsy confirmed
adenocarcinoma of duodenum/ampulla. Patient was deemed to be a high-risk candidate for Whipple’s procedure. The case was discussed in multidisciplinary tumor board and the patient was offered concurrent chemotherapy and radiation with capecitabine 500 mg BID. Posttreatment
CT scans suggested 60% shrinkage in tumor size. Patient was continued on capecitabine 300 mg BID two weeks on and one week off with continued response noted on restaging CT scans.

Case Report 2: A 76-year-old male with end stage renal disease on hemodialysis complained of bleeding per rectum for over 2 years. A colonoscopy showed a circumferential mass at 15 cm from anal verge, and biopsy was consistent with rectal adeno carcinoma. PET/CT scan confirmed primary lesion in rectum as well as abnormal retroperitoneal and left iliac adenopathy with high FDG uptake. EUS staged disease at uT3N0Mx. Given significant pain and bleeding patient was offered palliative radiation along with low dose capecitabine 500 mg BID. Two months after concurrent chemotherapy and radiation, restaging scans showed 50% shrinkage in primary tumor. The patient opted to continue treatment with capecitabine and completed two more cycles of 300 mg BID two weeks on and one week off. A repeat CT scan showed near complete resolution of rectal mass and lymphadenopathy.

Conclusions: Capecitabine is converted to active form 5-FU in liver by thymidine phosphorylase. Over 95% of the drug is excreted in urine. In the original phase II trial utilizing capecitabine at 1250 mg/m2 BID, four patients with GFR < 30 ml/min noted to have grade 3-4 toxicities. Jhaveri et al. in their retrospective analysis showed 12 patients tolerated reduced doses.

Background: Capecitabine is an oral precursor of 5-FU (5' deoxy-5-fluoridine), a commonly prescribed chemotherapeutic agent to treat gastrointestinal and breast cancers. Capecitabine is currently contraindicated in patients with severe renal failure with Glomerular filtration rate <
30 ml/min. Literature review shows limited evidence in safety and effectiveness of using capecitabine in patients undergoing hemodialysis.

Case Report 1: A 75-year-old old male with a history of end stage renal disease on hemodialysis, was diagnosed with a 10 cm duodenal mass on CT scan when presented with three months history of abdominal pain and 45 lb weight loss. esophagogastroduodenoscopy and biopsy confirmed
adenocarcinoma of duodenum/ampulla. Patient was deemed to be a high-risk candidate for Whipple’s procedure. The case was discussed in multidisciplinary tumor board and the patient was offered concurrent chemotherapy and radiation with capecitabine 500 mg BID. Posttreatment
CT scans suggested 60% shrinkage in tumor size. Patient was continued on capecitabine 300 mg BID two weeks on and one week off with continued response noted on restaging CT scans.

Case Report 2: A 76-year-old male with end stage renal disease on hemodialysis complained of bleeding per rectum for over 2 years. A colonoscopy showed a circumferential mass at 15 cm from anal verge, and biopsy was consistent with rectal adeno carcinoma. PET/CT scan confirmed primary lesion in rectum as well as abnormal retroperitoneal and left iliac adenopathy with high FDG uptake. EUS staged disease at uT3N0Mx. Given significant pain and bleeding patient was offered palliative radiation along with low dose capecitabine 500 mg BID. Two months after concurrent chemotherapy and radiation, restaging scans showed 50% shrinkage in primary tumor. The patient opted to continue treatment with capecitabine and completed two more cycles of 300 mg BID two weeks on and one week off. A repeat CT scan showed near complete resolution of rectal mass and lymphadenopathy.

Conclusions: Capecitabine is converted to active form 5-FU in liver by thymidine phosphorylase. Over 95% of the drug is excreted in urine. In the original phase II trial utilizing capecitabine at 1250 mg/m2 BID, four patients with GFR < 30 ml/min noted to have grade 3-4 toxicities. Jhaveri et al. in their retrospective analysis showed 12 patients tolerated reduced doses.

Background: Capecitabine is an oral precursor of 5-FU (5' deoxy-5-fluoridine), a commonly prescribed chemotherapeutic agent to treat gastrointestinal and breast cancers. Capecitabine is currently contraindicated in patients with severe renal failure with Glomerular filtration rate <
30 ml/min. Literature review shows limited evidence in safety and effectiveness of using capecitabine in patients undergoing hemodialysis.

Case Report 1: A 75-year-old old male with a history of end stage renal disease on hemodialysis, was diagnosed with a 10 cm duodenal mass on CT scan when presented with three months history of abdominal pain and 45 lb weight loss. esophagogastroduodenoscopy and biopsy confirmed
adenocarcinoma of duodenum/ampulla. Patient was deemed to be a high-risk candidate for Whipple’s procedure. The case was discussed in multidisciplinary tumor board and the patient was offered concurrent chemotherapy and radiation with capecitabine 500 mg BID. Posttreatment
CT scans suggested 60% shrinkage in tumor size. Patient was continued on capecitabine 300 mg BID two weeks on and one week off with continued response noted on restaging CT scans.

Case Report 2: A 76-year-old male with end stage renal disease on hemodialysis complained of bleeding per rectum for over 2 years. A colonoscopy showed a circumferential mass at 15 cm from anal verge, and biopsy was consistent with rectal adeno carcinoma. PET/CT scan confirmed primary lesion in rectum as well as abnormal retroperitoneal and left iliac adenopathy with high FDG uptake. EUS staged disease at uT3N0Mx. Given significant pain and bleeding patient was offered palliative radiation along with low dose capecitabine 500 mg BID. Two months after concurrent chemotherapy and radiation, restaging scans showed 50% shrinkage in primary tumor. The patient opted to continue treatment with capecitabine and completed two more cycles of 300 mg BID two weeks on and one week off. A repeat CT scan showed near complete resolution of rectal mass and lymphadenopathy.

Conclusions: Capecitabine is converted to active form 5-FU in liver by thymidine phosphorylase. Over 95% of the drug is excreted in urine. In the original phase II trial utilizing capecitabine at 1250 mg/m2 BID, four patients with GFR < 30 ml/min noted to have grade 3-4 toxicities. Jhaveri et al. in their retrospective analysis showed 12 patients tolerated reduced doses.

Background: Salivary gland carcinoma is a rare type of cancer, and when metastasized is associated with poor prognosis. Response rates to standard chemotherapy are less (15-30%) and usually short-lived. Salivary gland tumors expressing HER2/neu have lately been recognized. We describe 2 cases of ERBB2 amplification identified by NGS testing with response to Anti Her-2 therapy.

Case 1: A 69-year-old male veteran was originally diagnosed with a left parotid gland carcinoma at pleomorphic adenoma in September 2015. Patient underwent surgery with a left parotidectomy 4 out of 85 lymph nodes were positive for metastasis (T3, N2b, Mx, G3, Stage IVA disease). Patient was offered adjuvant chemo/XRT but was lost to follow-up. In October 2016, patient presented with recurrent left parotid gland swelling staging workup revealed diffuse metastatic disease to liver and bone. Patient had a palliative resection of the left parotid mass tumor was consistent with carcinoma and was offered palliative chemotherapy with carbo platinum and Taxol. After 4 cycles of chemotherapy repeat PET CT scan revealed progression of disease with new sternal, T3 vertebral, right sacral and numerous liver and upper abdominal lymph nodes. Next generation sequencing (NGS) by Foundation One revealed ERBB2/HER2 mutation. Patient was started on second-line palliative chemotherapy utilizing docetaxel and Herceptin every 3 weeks. After 3 cycles restaging PET CT scan showed good partial response in bone and stable disease in the liver.

Case 2: A 73-year-old male presented on 4/16 with rapidly enlarging recurrent mass and bone pain one year after right radical neck dissection followed by adjuvant XRT. Pathology demonstrated salivary gland adenocarcinoma. PET/CT: extensive axial and appendicular skeletal metastasis with widespread bony pain. NGS testing of the original pathology with Foundation One revealed ERBB2 amplification as well as alteration of PTEN and TP53. Patient was offered Carboplatin + Herceptin which he received and tolerated well. Pain resolved after 1st cycle. Metabolic PR by PET/CT was noted after 4 cycles.

Conclusions: Adding trastuzumab to chemotherapy in patients with Her2/neu-positive metastatic salivary gland carcinoma gave promising results. Our institutional experience matches with few other case reports/series published to date. Validating this results with a randomized study would be a challenge, given the rarity of this disease.

Background: Salivary gland carcinoma is a rare type of cancer, and when metastasized is associated with poor prognosis. Response rates to standard chemotherapy are less (15-30%) and usually short-lived. Salivary gland tumors expressing HER2/neu have lately been recognized. We describe 2 cases of ERBB2 amplification identified by NGS testing with response to Anti Her-2 therapy.

Case 1: A 69-year-old male veteran was originally diagnosed with a left parotid gland carcinoma at pleomorphic adenoma in September 2015. Patient underwent surgery with a left parotidectomy 4 out of 85 lymph nodes were positive for metastasis (T3, N2b, Mx, G3, Stage IVA disease). Patient was offered adjuvant chemo/XRT but was lost to follow-up. In October 2016, patient presented with recurrent left parotid gland swelling staging workup revealed diffuse metastatic disease to liver and bone. Patient had a palliative resection of the left parotid mass tumor was consistent with carcinoma and was offered palliative chemotherapy with carbo platinum and Taxol. After 4 cycles of chemotherapy repeat PET CT scan revealed progression of disease with new sternal, T3 vertebral, right sacral and numerous liver and upper abdominal lymph nodes. Next generation sequencing (NGS) by Foundation One revealed ERBB2/HER2 mutation. Patient was started on second-line palliative chemotherapy utilizing docetaxel and Herceptin every 3 weeks. After 3 cycles restaging PET CT scan showed good partial response in bone and stable disease in the liver.

Case 2: A 73-year-old male presented on 4/16 with rapidly enlarging recurrent mass and bone pain one year after right radical neck dissection followed by adjuvant XRT. Pathology demonstrated salivary gland adenocarcinoma. PET/CT: extensive axial and appendicular skeletal metastasis with widespread bony pain. NGS testing of the original pathology with Foundation One revealed ERBB2 amplification as well as alteration of PTEN and TP53. Patient was offered Carboplatin + Herceptin which he received and tolerated well. Pain resolved after 1st cycle. Metabolic PR by PET/CT was noted after 4 cycles.

Conclusions: Adding trastuzumab to chemotherapy in patients with Her2/neu-positive metastatic salivary gland carcinoma gave promising results. Our institutional experience matches with few other case reports/series published to date. Validating this results with a randomized study would be a challenge, given the rarity of this disease.

Background: Salivary gland carcinoma is a rare type of cancer, and when metastasized is associated with poor prognosis. Response rates to standard chemotherapy are less (15-30%) and usually short-lived. Salivary gland tumors expressing HER2/neu have lately been recognized. We describe 2 cases of ERBB2 amplification identified by NGS testing with response to Anti Her-2 therapy.

Case 1: A 69-year-old male veteran was originally diagnosed with a left parotid gland carcinoma at pleomorphic adenoma in September 2015. Patient underwent surgery with a left parotidectomy 4 out of 85 lymph nodes were positive for metastasis (T3, N2b, Mx, G3, Stage IVA disease). Patient was offered adjuvant chemo/XRT but was lost to follow-up. In October 2016, patient presented with recurrent left parotid gland swelling staging workup revealed diffuse metastatic disease to liver and bone. Patient had a palliative resection of the left parotid mass tumor was consistent with carcinoma and was offered palliative chemotherapy with carbo platinum and Taxol. After 4 cycles of chemotherapy repeat PET CT scan revealed progression of disease with new sternal, T3 vertebral, right sacral and numerous liver and upper abdominal lymph nodes. Next generation sequencing (NGS) by Foundation One revealed ERBB2/HER2 mutation. Patient was started on second-line palliative chemotherapy utilizing docetaxel and Herceptin every 3 weeks. After 3 cycles restaging PET CT scan showed good partial response in bone and stable disease in the liver.

Case 2: A 73-year-old male presented on 4/16 with rapidly enlarging recurrent mass and bone pain one year after right radical neck dissection followed by adjuvant XRT. Pathology demonstrated salivary gland adenocarcinoma. PET/CT: extensive axial and appendicular skeletal metastasis with widespread bony pain. NGS testing of the original pathology with Foundation One revealed ERBB2 amplification as well as alteration of PTEN and TP53. Patient was offered Carboplatin + Herceptin which he received and tolerated well. Pain resolved after 1st cycle. Metabolic PR by PET/CT was noted after 4 cycles.

Conclusions: Adding trastuzumab to chemotherapy in patients with Her2/neu-positive metastatic salivary gland carcinoma gave promising results. Our institutional experience matches with few other case reports/series published to date. Validating this results with a randomized study would be a challenge, given the rarity of this disease.