Retreatment with agents to which patients have shown secondary resistance or a mixed response is usually avoided by oncologists, though recent results suggest that continuing herceptin after secondary resistance is associated with a better outcome than discontinuation. Here we present preliminary results of a pilot study in which patients were retreated with agents that had previously produced prolonged stable disease (SD), partial or complete remission (PR/CR) or a mixed response,followed by progression.This study was performed according the guidelines of the MD Anderson Cancer Center Institutional Review Board.

Eleven patients with diverse, advanced cancers (median number of prior systemic therapies in the metastatic setting = four (range, 2-7) have been included to date (number of men = 8; median age = 57 years; median ECOG performance status = 1)., The median duration between the initial treatment and the retreatment regimen was 95 weeks (range 5-323 weeks). Eight of 11patients (73%) on a retreatment regimen showed stable disease (SD) >24 weeks or a partial response. Of these eight, two were retreated with precisely the same agent(s); one, with a different agent that has the same mechanism of action (EGFR inhibitor; gefitinib first and then erlotinib); and five, with the same agent(s) but with additional agents added.

NDiagnosisNo of prior therapiesBest Prior TreatmentGap* (weeks)Best Retreatment
NameDuration(weeks)Best ResponseNameDuration (weeks)Best Response
Adenocystic Carcinoma Erlotinib 99 PR 54 Erlotinib 69 SD 
Hepatic Cholangiocarcinoma Sorafenib Mixed 15 Bevacizumab plus Sorafenib 36 SD 
Myxoid Liposarcoma Trabectedin 58 SD 92 Trabectedin PD 
Ewing's Sarcoma IGF inhibitor 148 PR IGF inhibitor plus mTOR inhibitor 153+ PR 
Rectal Adenocarcinoma Capecitabine plus bevacizumab 44 SD 95 Capecitabine plus Bevacizumab 24 SD 
Ovarian Serous Carcinoma Paclitaxel plus carboplatin 18 CR 120 Paclitaxel and Carboplatin (Bevacizumab added after 4 months) 60+ PR 
Colorectal Cancer FOLFOX plus bevacizumab 22 CR 26 HAI Oxaliplatin plus HAI Irinotecan plus IV Bevacizumab PD 
Squamous Cell Cancer of Head and Neck Chemoradiation with Carboplatin and taxane CR 214 Docetaxel plus Carboplatin plus 5FU PR 
Colorectal Adenocarcinoma FOLFIRI plus bevacizumab 24 PR 104 HAI Oxaliplatin and IV Bevacizumab and PO Capecitabine 12 SD 
10 Adenocystic Carcinoma Gefitinib 114 SD 322 Erlotinib 31+ SD 
11 Invasive Ductal Carcinoma of Breast Carboplatin plus Docetaxel plus Herceptin 21 CR 383 Carboplatin, Taxotere, Herceptin and Temsirolimus 26 PR 
NDiagnosisNo of prior therapiesBest Prior TreatmentGap* (weeks)Best Retreatment
NameDuration(weeks)Best ResponseNameDuration (weeks)Best Response
Adenocystic Carcinoma Erlotinib 99 PR 54 Erlotinib 69 SD 
Hepatic Cholangiocarcinoma Sorafenib Mixed 15 Bevacizumab plus Sorafenib 36 SD 
Myxoid Liposarcoma Trabectedin 58 SD 92 Trabectedin PD 
Ewing's Sarcoma IGF inhibitor 148 PR IGF inhibitor plus mTOR inhibitor 153+ PR 
Rectal Adenocarcinoma Capecitabine plus bevacizumab 44 SD 95 Capecitabine plus Bevacizumab 24 SD 
Ovarian Serous Carcinoma Paclitaxel plus carboplatin 18 CR 120 Paclitaxel and Carboplatin (Bevacizumab added after 4 months) 60+ PR 
Colorectal Cancer FOLFOX plus bevacizumab 22 CR 26 HAI Oxaliplatin plus HAI Irinotecan plus IV Bevacizumab PD 
Squamous Cell Cancer of Head and Neck Chemoradiation with Carboplatin and taxane CR 214 Docetaxel plus Carboplatin plus 5FU PR 
Colorectal Adenocarcinoma FOLFIRI plus bevacizumab 24 PR 104 HAI Oxaliplatin and IV Bevacizumab and PO Capecitabine 12 SD 
10 Adenocystic Carcinoma Gefitinib 114 SD 322 Erlotinib 31+ SD 
11 Invasive Ductal Carcinoma of Breast Carboplatin plus Docetaxel plus Herceptin 21 CR 383 Carboplatin, Taxotere, Herceptin and Temsirolimus 26 PR 

*Gap in weeks between the previous treatment and initiation of the retreatment with some of the same drugs.

Our pilot data suggest that retreatment with agents to which patients had previously shown durable SD/CR/PR or mixed response followed by secondary resistance can produce SD > = 24 weeks/ PR when given alone or in combination after a gap between initial treatment and retreatment. Plausible mechanisms accounting for this phenomenon include persistence of a suppressed clone alongside the new resistant clone, drug synergy,and epigenetic modulation during drug holidays. Further investigation of the effect of retreatment in patients with advanced metastatic disease is warranted.

Citation Format: Rishi Agarwal, Aung Naing, Gerald Falchook, Jennifer Wheler, Siqing Fu, Razelle Kurzrock. Retreatment after secondary resistance: A pilot study. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1177. doi:10.1158/1538-7445.AM2013-1177