title: Chemotherapy rechallenge after regorafenib treatment in metastatic colorectal cancer: still hope after the last hope?
abstract: BACKGROUND
  The introduction of biological agents in cancer therapy is changing the progression of metastatic colorectal cancer. Currently, resistance to biological agents is an emerging problem; the progression of the disease is caused by the development of resistant clones. According to some authors, these clones can be re-sensitized to traditional and previously utilized chemotherapy agents. The results of the CORRECT study demonstrated the efficacy of regorafenib monotherapy in both KRAS wild type and mutant pretreated patients (pts). Two recent reports showed the potential of reintroduction of chemotherapy, even after treatment with regorafenib.
  
  
  METHODS
  We performed a retrospective review of clinical data from patients treated with regorafenib at our institution between March 2012 and March 2013. We analysed patient characteristics, KRAS/NRAS status, response to treatment (evaluated by RECIST v1.1 criteria) and survival.
  
  
  RESULTS
  Regorafenib was administered to 128 patients, and 11 (8.6%) received post-regorafenib therapy (to our knowledge). Seven (63.6%) patients were wild type for KRAS/NRAS. Post-regorafenib therapy represented for all the patients at least the fourth line: all the pts received both oxaliplatin- and irinotecan-based chemotherapy, all of them were treated with bevacizumab, and 7 patients also received cetuximab. Eight patients (72.7%) were treated with standard chemotherapy after regorafenib (irinotecan monotherapy, capecitabine plus oxaliplatin or irinotecan, dacarbazine or raltitrexed), while 3 patients received an experimental therapy (clinical trial). Nine of the 11 (81.8%) patients had PD and 2 patients had SD. The median progression-free survival was 1.6+ months (range 0.5-3.5), the median OS post-regorafenib was 2.1+ months (range 0.5-10.2) and the 6-month OS was 27.3%.
  
  
  CONCLUSIONS
  Our retrospective analysis showed that after regorafenib therapy, re-introduction of chemotherapy is possible. Unfortunately, we reported a high percentage of disease progression beyond regorafenib, which is likely due to the high percentage of heavily pretreated patients (some received four or five types of therapy before regorafenib). We think that regorafenib could represent a chemotherapy resensitizing agent; however, additional studies are needed in patients who have received less pretreatment.
authors.affiliation: a Medical Oncology Unit , Fondazione Poliambulanza , Brescia , Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Bertocchi
authors.affiliation: a Medical Oncology Unit , Fondazione Poliambulanza , Brescia , Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Aroldi
authors.affiliation: a Medical Oncology Unit , Fondazione Poliambulanza , Brescia , Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Prochilo
authors.affiliation: a Medical Oncology Unit , Fondazione Poliambulanza , Brescia , Italy.
authors.forename: Fausto
authors.initials: F
authors.lastname: Meriggi
authors.affiliation: b Medical Oncology Unit , Humanitas Gavazzeni , Bergamo , Italy.
authors.forename: Giordano Domenico
authors.initials: GD
authors.lastname: Beretta
authors.affiliation: a Medical Oncology Unit , Fondazione Poliambulanza , Brescia , Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Zaniboni
mesh_terms: D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000068818:Cetuximab / Q000008:administration & dosage; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010671:Phenylurea Compounds / Q000008:administration & dosage; D011379:Prognosis; D011725:Pyridines / Q000008:administration & dosage; D012189:Retrospective Studies; D015996:Survival Rate
chemical_list: D009944:Organoplatinum Compounds; D010671:Phenylurea Compounds; D011725:Pyridines; D000077150:Oxaliplatin; C559147:regorafenib; D000068258:Bevacizumab; D000077146:Irinotecan; D000068818:Cetuximab; D005472:Fluorouracil; D002166:Camptothecin
keywords: Chemotherapy rechallenge; Colon cancer; Regorafenib