Class / Drug / Setting / Study type / Number of patients / Median interval between initial and retreatment (months) / Intervening therapy / Initial response / Rechallenge response / PFS or TTP (months) / OS from start of rechallenge (months) / Reference
Original cohort / Rechallenged+evaluable for response / %ORR / %SD / %ORR / %SD / Initial / Rechallenge
Monoclonal antibody/anti-CD52 / Alemtuzumab / Bcell CLL / Retrospective / 17 / 17 / 10.2 / No / __ / __ / 53§ / 18 / __ / __ / 16.7 / Fiegl 20071
Monoclonal antibody/anti-CD52 / Alemtuzumab / Bcell CLL / Retrospective, international multicentre / 30 / 30 / 10.9 / No / 43.3 / 36.7 / 48.3 / 20.7 / 8.9 / 6.3 / 20 / Fiegl 20112
Monoclonal antibody /anti-VEGF / Bevacizumab / Epithelial ovarian carcinoma / PhaseII prospective / 5 / 5 / (Range 629months in 4pts) / No / 100PR or SD / 100PR or SD / 40 / 40 / __ / __ / 4pts no PD >18weeks / Konstantinopoulos 20123
Proteasome inhibitor / Bortezomib / Relapsed Multiple Myeloma / Retrospective / 11 / 10 / __ / No / 100 SD / 0 / 60 / 40 / __ / 9 / __ / Ciolli 20074
Proteasome inhibitor / Bortezomib / Relapsed Multiple Myeloma / Prospective, PhaseIV / 124 / 32 / 9.9 / No / 100 / 0 / 50 / 16 / 27.2 / 6.6 / __ / Sood 20095
Proteasome inhibitor / Bortezomib / Relapsed Multiple Myeloma / Retrospective / 60 / 60 / 8.6 / Yes, various (13.3%) / 100 / 0 / 63.3 / 16.7 / 10.9 / 9.3 / 20.4 / Hrusovsky 20106
Proteasome inhibitor / Bortezomib / First line Multiple myeloma / Multicentre Retrospective / 178 / 43 / 17.6‡ / No / 100 / 0 / 41 / __ / __ / __ / __ / Mateos 20107
Proteasome inhibitor / Bortezomib / Relapsed Multiple Myeloma / Prospective international PhaseII / 130 / 126 / ≥6 / No / 100 / 0 / 40 / 18 (minimal response) / __ / 8.38 / __ / Petrucci 20138
Proteasome inhibitor / Bortezomib / Relapsed Multiple Myeloma / Multicentre retrospective / 43 / 40 / 8.9 / Yes, various (28.6%) / 100 / 0 / 64.3 / 19 / 10.7 / 10.5 / 20.4 / Taverna 20129
Microtubule inhibitor - taxane / Docetaxel(± calcitriol) / Castration resistant prostate cancer / Prospective, phaseII extension trial / 8 / 7 / 4.6‡ / No / 100 / 0 / 57.1 / 42.9 / __ / __ / __ / Beer 200310
Microtubule inhibitor - taxane / Docetaxel(± calcitriol) / Castration resistant prostate cancer / Prospective multicentre phaseIII extension trial / 45 / 36 / 4.1‡ / No / 100 / 0 / 45.5 / 45.5 / __ / __ / __ / Beer 200811
Microtubule inhibitor - taxane / Docetaxel / Castration resistant prostate cancer / Retrospective / 25 / 5 / 11.8 / No / 92 (PSA ≥50%) / 4 (30% ≥PSA<50%) / 32 (PSA ≥ 50%) / 20 (30% ≥PSA
<50%) / __ / 8 / 9.6 / Jancovic 200812
Microtubule inhibitor - taxane / Docetaxel / Castration resistant prostate cancer / Retrospective / 10 / 10 / 5.5 / No / 70 (PSA≥50%) / 20 / 70 (PSA ≥ 50%) / 0 / __ / __ / __ / Ansari 200813
Microtubule inhibitor - taxane / Docetaxel(± estramustine) / Castration resistant prostate cancer / Retrospective / 39 / 39 / 3 / No / 90 (PSA≥50%) / 10 / 38 (PSA≥ 50%) / 26 (30% ≥PSA
<50%) / 7.8 / 4.3 / 16 / Loriot 201014
Microtubule inhibitor - taxane / Docetaxel(+ estramustine or capecitabine 68%) / Castration resistant prostate cancer / Retrospective / 50 / 50 / 18.4 / No / 100 / 0 / 48 (PSA≥ 50%) / 36+14 (30% ≥PSA<50%) / 10.3 / __ / 16 / Eymard 201015
Microtubule inhibitor - taxane / Docetaxel+prednisone / Castration resistant prostate cancer / Prospective multicentre phaseII / 45 / 45 / 7 / No / 100 / 0 / 24.5 / 11.1+11.1 (minor PSA changes) / __ / 5 / 13 / Di Lorenzo 201116
Microtubule inhibitor - taxane / Docetaxel / Castration resistant prostate cancer / Retrospective / 43 / 43 / 5 / No / 82 (PSA ≥50%) / __ / 28 (of initial responders) / __ / __ / 5.9 / 21.8 / Heck 201217
Platinum-based combination chemotherapy / FOLFOX (various regimens) / Advanced colorectal carcinoma / Retrospective / 104 / 29 / 6.9 / Yes (55% 5FU or irinotecan) / 83 / 14 / 21 / 52 / 7.6 / 4.1 / 9.7 / Maindrault-Goebel 200418
Platinum-based combination chemotherapy / FOLFOX (FOLFOX7 regimen) / Advanced colorectal carcinoma / Prospective randomized phaseII / 124 / 89 / 5.5 (pre-planned) / Yes (fluorouracil+leucovorin) / 61.8* / 28.4* / 7.1* / 45.2* / 8.7‡ / __ / 21.2‡ / Tournigand 200619
Platinum-based combination chemotherapy / FOLFOX (FOLFOX7 regimen) / Advanced colorectal carcinoma / Prospective randomized phaseII / 104 / 66 (no maintenance arm) / 3.9 / No / 59.6 / 40.4 / 30.3 / 27.3 / 6.6 / 3.9 / 19.5 / Chibaudel 200920
Platinum or irinotecan-based chemotherapy / FOLFIRI or FOLFOX / Advanced colorectal carcinoma / Retrospective / 13 / 13 / __ / Yes, all (FOLFOX or FOLFIRI) / __ / __ / 0 / 38 / __ / __ / __ / Hsu 200921
Platinum-based chemotherapy / Fluorouracil or capecitabine and oxaliplatin / Advanced colorectal carcinoma / Prospective randomized phaseIII / 511 / 268 / 3.7 / No / 57.4* / 27.3* / 32.8 / 38.4 / 3.0‡ / __ / 18 / Adams 201122
Platinum-based chemotherapy / FOLFOXIRI / Advanced colorectal carcinoma / Retrospective, multi-trial / 136 / 32 / 6.1 / No / 91 / 9 / 38 / __ / 9.9‡ / 8.2 / 19.3 / Fornaro 201223
Tyrosine kinase/BCR-ABL inhibitor / Imatinib / Chronic myelogenous leukemia / Prospective phaseII / 12 / 6 / 2.5 / No / 100 – all CMR / 0 / 100 – includes 33.3% CMR / 0 / 32‡
+2.5 / (No PD – 18 mo med. follow-up) / __ / Rousselot 200724
Tyrosine kinase/BCR-ABL inhibitor / Imatinib / Chronic myelogenous leukemia / Retrospective / 26 / 24 / 7 / No / 100 – all CMR / 0 / 95.8 – molecular/cytogenetic CR / 0 / 9.5+7 (duration of therapy+time to relapse) / (96% No PD 44 mo med. follow-up) / __ / Goh 200926
Tyrosine kinase/BCR-ABL inhibitor / Imatinib / Chronic myelogenous leukemia / Prospective multicentre phaseII / 69 / 42 / 2 / No / 100 – all CMR / 0 / 100 – includes 62% CMR / 0 / 35.5 (CMR duration before imatinib discontinued) / (No PD last follow-up) / __ / Mahon 201027
Tyrosine kinase/BCR-ABL inhibitor / Imatinib / Chronic myelogenous leukemia / Prospective phaseII / 40 / 22 / __ / No / 100(CMR) / 0 / 100 (CMR) / 0 / __ / __ / __ / Ross 201325
Tyrosine kinase/KIT inhibitor / Imatinib / Gastrointestinal stromal tumour / Prospective / 14 / 9 / 10.1 / No / 85.7‡ / 14.3‡ / 55.6 / 33.3 / 21.8‡ / (1yr PFS 78%) / (2yr OS 92.3%) / Lee 200628
Tyrosine kinase/KIT inhibitor / Imatinib / Gastrointestinal stromal tumour / Prospective, randomized phaseIII / 32 / 26 / __ / No / 72.4* / 27.6* / 92 OR+SD / 92 OR+SD / __ / __ / (ns. vs. continuous group) / 2007 Blay29
Tyrosine kinase/KIT inhibitor / Imatinib / Gastrointestinal stromal tumour / Prospective, randomized phaseIII / 25 / 20 / 9 / No / 85 / 15 / 60 / 40 / 36+9 (duration of therapy+time to relapse) / (6/20 PD at 24.9 mo) / (2yr OS 96%) / Le Cesne 201030
Tyrosine kinase/KIT inhibitor / Imatinib / Gastrointestinal stromal tumour / Prospective, randomized phaseIII / 81 / 46‡ / __ / No / __ / __ / 63.0 / 21.7 / N/A – adjuvant imatinib / 35.7 (1 and 3yr treatment) / __ / Reichardt 201131
Monoclonal antibody/anti-CD20 / Rituximab / Non-Hodgkin lymphoma / Prospective PhaseII / 60 / 57 / 14.5 / No / 100 / 0 / 40 / __ / 12.4 / 17.8 (estimated) / __ / Davis 200032
Monoclonal antibody/anti-CD20 / Rituximab / Non-Hodgkin lymphoma / PhaseII Prospective / 13 / 13 / __ / No / 85 / 15 / 38 / 46 / 8.2 / 5.1 / (93% at 19 mo) / Igarashi 200133
Monoclonal antibody/anti-CD20 / Rituximab / Non-Hodgkin lymphoma / Retrospective / 41 / 11 / 15.5‡ / No / __ / __ / 54.5 / 36.4 / 11.3‡ / 15.2‡ / __ / Lemieux 200434
Monoclonal antibody/anti-CD20 / Rituximab / Non-Hodgkin lymphoma / PhaseII Randomized / 46 / 27 / __ / No / 33 / 67‡ / 35 / 65 / 7.4 / __ / (68% at 3yr) / Hainsworth 200535
Monoclonal antibody/anti-CD20 / Rituximab / B-cell lymphoma (relapsed and refractory) / Single centre retrospective case control / 178 / 12 / __ / No / __ / __ / 66 / _’_ / 13.2‡ / 12.5‡ / 19 / Johnston 201036
Monoclonal antibody/anti-CD20 / Rituximab / Non-Hodgkin lymphoma / PhaseIII randomized prospective / 134 / 134 / __ / No / 71 / 29 / __ / __ / __ / (3.6yr TTTF) / __ / Kahl 201137
Alkylating agent / Temozolomide, 93% same regimen / Malignant glioma / Retrospective / 14 / 13 / 12 / Yes (5 curmustine and surgery) / 44* / 56* / 28 / 14 / 21 / 3 / __ / Franceschi 200538
Alkylating agent / Temozolomide, different regimens / Malignant glioma / Retrospective / 8 / 8 / __ / No / 37.5 / 50 / 75 / 25 / __ / __ / __ / 2006 Balmaceda39
Alkylating agent / Temozolomide, different regimen / Malignant glioma / Prospective / 12 / 12 / N/A (pts mix progressed and relapsed) / No / __ / __ / 16.7 / 41.7 / __ / 6 / 11 / Kong 200640
Alkylating agent / Temozolomide, different regimens / Malignant glioma / Retrospective / 14 / 14 / 3 / No / 100PR or SD / 100PR or SD / 14 / 64 / __ / (6 mo 57%) / __ / Perry 200841
Alkylating agent / Temozolomide, different regimen / Malignant glioma / Prospective / 21 / 21 / Most <3 / Yes (10% procarbazine and CCNU) / __ / __ / 22 / 39 / 8.2 / (6 mo 39%) / 9.1 / Strik 200842
Alkylating agent / Temozolomide, different regimen / Malignant glioma / Retrospective / 80 / 22 (gr.III), 45 (gr.IV)- incl. 25 PD on therapy / >1.84 / Yes (71% resections) / 55/10 (grade III/IV) ‡ / 32/62 (grade III/IV) ‡ / 32.0/10.4 (grade III/IV) / 36.0/58.3 (grade III/IV) / 17.7/9.4 (grade III/IV) ‡ / 7.6/4.9 (grade III/IV) / 19.0/5.3 (grade III/IV) / Wick 200943
Alkylating agent / Temozolomide, different regimen / Malignant glioma / Prospective phaseII / 116 / 28 / >2 / No / __ / __ / 11.1 / 25.9 / __ / 3.7 (6 mo 35.7%) / (60.7% 1yr OS) / Perry 201044
Tetrahydroisoquinoline alkaloid / Trabectedin / Advanced soft tissue sarcoma / Retrospective / 8 / 8 / __ / No / 62.5 / 37.5 / 50 / 50 / 24 / (Not reached med follow-up 7 mo) / __ / Sanfilippo 200945
Tetrahydroisoquinoline alkaloid / Trabectedin / Advanced soft tissue sarcoma / Retrospective / 18 / 12 / __ / Yes (surgery7pts) / 66.7 / 33.3 / 58.3 / 41.7 / __ / 14 / __ / Sanfilippo 201046
Rechallenge patient numbers reflect those patients receiving both initial and rechallenge therapy that were evaluable for response. Other cases are noted.When appropriate weeks converted into months: 1week=0.229,984months, days converted into months: 1day=0.0328,549months. * Calculation includes patients evaluable for response, excludes patients not assessable or data missing. ‡data based on original cohort of patients/intent to treat population. Patients received initial therapy, but not all were rechallenged (due to lack of PD or patients not evaluable for response). § Response rates include 12% of patients that died early and were not evaluable for response
Abbreviations: CMR, complete molecular response; med., median; ns, not significant; OR, objective response; ORR, overall response rate=PR (partial response)+CR (complete response);PR, partial response;CR, complete response; PD, progressive disease; PFS, progression-free survival; pts, patients; PSA, prostate specific antigen; SD, stable disease; TTP, time to progression; TTTF, time to treatment failure
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