Mitomycin C in Homologous Recombination Deficient Metastatic Pancreatic Cancer after Disease Progression on Platinum-Based Chemotherapy and Olaparib
Recent efforts to personalize treatment with platinum-based chemotherapy and PARP inhibitors have produced promising results in homologous recombinant deficient (HRD) metastatic pancreatic cancer (MPC). However, new strategies are necessary to overcome resistance. The below case series documents pat...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-10-01
|
| Series: | Biomedicines |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2227-9059/10/11/2705 |
| _version_ | 1797469035520065536 |
|---|---|
| author | Gehan Botrus Denise Roe Gayle S. Jameson Pedro Luiz Serrano Uson Junior Ronald Lee Korn Lana Caldwell Taylor Bargenquast Max Miller Erkut Hasan Borazanci |
| author_facet | Gehan Botrus Denise Roe Gayle S. Jameson Pedro Luiz Serrano Uson Junior Ronald Lee Korn Lana Caldwell Taylor Bargenquast Max Miller Erkut Hasan Borazanci |
| author_sort | Gehan Botrus |
| collection | DOAJ |
| description | Recent efforts to personalize treatment with platinum-based chemotherapy and PARP inhibitors have produced promising results in homologous recombinant deficient (HRD) metastatic pancreatic cancer (MPC). However, new strategies are necessary to overcome resistance. The below case series documents patients treated at the HonorHealth Research Institute with a diagnosis of HRD MPC who received Mitomycin C (MMC) treatment from January 2013 until July 2018. Five HRD MPC patients treated with MMC were evaluated. All patients received at least one course of treatment. Mean age at MMC treatment initiation was 58 years. There were 3 females and 2 males. All patients had tumors that progressed on platinum-based chemotherapy, four patients had previous exposure to Olaparib. The median PFS was 10.1 months, and the median OS was 12.3 months. Responses were observed only in patients harboring <i>BRCA2</i> mutations, no response was observed in the <i>PALB2</i> mutation carrier. MMC in this heavily previously treated PC was safe, with overall manageable grade 2 gastrointestinal toxicities including nausea and vomiting, and G3 hematological toxicities including anemia and thrombocytopenia. Pancreatic cancer patients with HRD may benefit from MMC treatment. Further clinical investigation of MMC in pancreatic cancer is warranted. |
| first_indexed | 2024-03-09T19:15:45Z |
| format | Article |
| id | doaj.art-fef31b1ea83f4b2a9cfb0217d4e2c537 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-09T19:15:45Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-fef31b1ea83f4b2a9cfb0217d4e2c5372023-11-24T03:49:22ZengMDPI AGBiomedicines2227-90592022-10-011011270510.3390/biomedicines10112705Mitomycin C in Homologous Recombination Deficient Metastatic Pancreatic Cancer after Disease Progression on Platinum-Based Chemotherapy and OlaparibGehan Botrus0Denise Roe1Gayle S. Jameson2Pedro Luiz Serrano Uson Junior3Ronald Lee Korn4Lana Caldwell5Taylor Bargenquast6Max Miller7Erkut Hasan Borazanci8HonorHealth Research Institute, Scottsdale, AZ 85258, USAUA Cancer Center, University of Arizona, Tucson, AZ 85719, USAHonorHealth Research Institute, Scottsdale, AZ 85258, USACenter for Personalized Medicine, Hospital Israelita Albert Einstein, São Paulo 05652-900, BrazilScottsdale Medical Imaging, Ltd., Scottsdale, AZ 85258, USAHonorHealth Research Institute, Scottsdale, AZ 85258, USAHonorHealth Research Institute, Scottsdale, AZ 85258, USAHonorHealth Research Institute, Scottsdale, AZ 85258, USAHonorHealth Research Institute, Scottsdale, AZ 85258, USARecent efforts to personalize treatment with platinum-based chemotherapy and PARP inhibitors have produced promising results in homologous recombinant deficient (HRD) metastatic pancreatic cancer (MPC). However, new strategies are necessary to overcome resistance. The below case series documents patients treated at the HonorHealth Research Institute with a diagnosis of HRD MPC who received Mitomycin C (MMC) treatment from January 2013 until July 2018. Five HRD MPC patients treated with MMC were evaluated. All patients received at least one course of treatment. Mean age at MMC treatment initiation was 58 years. There were 3 females and 2 males. All patients had tumors that progressed on platinum-based chemotherapy, four patients had previous exposure to Olaparib. The median PFS was 10.1 months, and the median OS was 12.3 months. Responses were observed only in patients harboring <i>BRCA2</i> mutations, no response was observed in the <i>PALB2</i> mutation carrier. MMC in this heavily previously treated PC was safe, with overall manageable grade 2 gastrointestinal toxicities including nausea and vomiting, and G3 hematological toxicities including anemia and thrombocytopenia. Pancreatic cancer patients with HRD may benefit from MMC treatment. Further clinical investigation of MMC in pancreatic cancer is warranted.https://www.mdpi.com/2227-9059/10/11/2705pancreatic cancerBRCAOlaparibhomologous recombination deficientmitomycin |
| spellingShingle | Gehan Botrus Denise Roe Gayle S. Jameson Pedro Luiz Serrano Uson Junior Ronald Lee Korn Lana Caldwell Taylor Bargenquast Max Miller Erkut Hasan Borazanci Mitomycin C in Homologous Recombination Deficient Metastatic Pancreatic Cancer after Disease Progression on Platinum-Based Chemotherapy and Olaparib Biomedicines pancreatic cancer BRCA Olaparib homologous recombination deficient mitomycin |
| title | Mitomycin C in Homologous Recombination Deficient Metastatic Pancreatic Cancer after Disease Progression on Platinum-Based Chemotherapy and Olaparib |
| title_full | Mitomycin C in Homologous Recombination Deficient Metastatic Pancreatic Cancer after Disease Progression on Platinum-Based Chemotherapy and Olaparib |
| title_fullStr | Mitomycin C in Homologous Recombination Deficient Metastatic Pancreatic Cancer after Disease Progression on Platinum-Based Chemotherapy and Olaparib |
| title_full_unstemmed | Mitomycin C in Homologous Recombination Deficient Metastatic Pancreatic Cancer after Disease Progression on Platinum-Based Chemotherapy and Olaparib |
| title_short | Mitomycin C in Homologous Recombination Deficient Metastatic Pancreatic Cancer after Disease Progression on Platinum-Based Chemotherapy and Olaparib |
| title_sort | mitomycin c in homologous recombination deficient metastatic pancreatic cancer after disease progression on platinum based chemotherapy and olaparib |
| topic | pancreatic cancer BRCA Olaparib homologous recombination deficient mitomycin |
| url | https://www.mdpi.com/2227-9059/10/11/2705 |
| work_keys_str_mv | AT gehanbotrus mitomycincinhomologousrecombinationdeficientmetastaticpancreaticcancerafterdiseaseprogressiononplatinumbasedchemotherapyandolaparib AT deniseroe mitomycincinhomologousrecombinationdeficientmetastaticpancreaticcancerafterdiseaseprogressiononplatinumbasedchemotherapyandolaparib AT gaylesjameson mitomycincinhomologousrecombinationdeficientmetastaticpancreaticcancerafterdiseaseprogressiononplatinumbasedchemotherapyandolaparib AT pedroluizserranousonjunior mitomycincinhomologousrecombinationdeficientmetastaticpancreaticcancerafterdiseaseprogressiononplatinumbasedchemotherapyandolaparib AT ronaldleekorn mitomycincinhomologousrecombinationdeficientmetastaticpancreaticcancerafterdiseaseprogressiononplatinumbasedchemotherapyandolaparib AT lanacaldwell mitomycincinhomologousrecombinationdeficientmetastaticpancreaticcancerafterdiseaseprogressiononplatinumbasedchemotherapyandolaparib AT taylorbargenquast mitomycincinhomologousrecombinationdeficientmetastaticpancreaticcancerafterdiseaseprogressiononplatinumbasedchemotherapyandolaparib AT maxmiller mitomycincinhomologousrecombinationdeficientmetastaticpancreaticcancerafterdiseaseprogressiononplatinumbasedchemotherapyandolaparib AT erkuthasanborazanci mitomycincinhomologousrecombinationdeficientmetastaticpancreaticcancerafterdiseaseprogressiononplatinumbasedchemotherapyandolaparib |