Table 1.
First author, year of publication | Pts enrolled | Phase | Target | Regimen | Clinical endopoint / ORR | Toxicity |
---|---|---|---|---|---|---|
Tewari., 2013 23 | 450 | III | VEGF | Bevacizumab (15 mg/kg iv every 21 days) with or without four chemotherapy regimens | OS 17 months in bevacizumab arms versus 13 months in the chemotherapy arms | Treatment with B was associated with more grade 3-4 bleeding (5 vs 1%) thrombosis/embolism (9 vs 2%), and GI fistula (3 vs 0%). |
Schefter, 2012 24 | 60 | II | VEGF | Bevacizumab (10 mg/kg iv every 2 weeks for three cycles) in combination with definitive radiotherapy and cisplatin chemotherapy | No data | 15 (31%) protocol-specified treatment-related AEs within 90 days of treatment start; the most common were hematologic (12/15; 80%). No treatment-related SAEs. |
Zighelboim, 2013 25 | 27 | II | VEGF | Bevacizumab (15mg/kg iv every 21days) with topotecan and cisplatin | ORR: 33.3% | Grade 3-4 hematologic toxicity was common (thrombocytopenia 82% leukopenia 74%, anemia 63%, neutropenia 56%). Most patients (78%) required unanticipated hospital admissions for supportive care and/or management of toxicities |
Mackay, 2010 26 | 19 | II | VEGF | Sunitinib 50 mg daily per os | No objective responses. Median TTP: 3.5 months. | High rate of fistula development (26%) |
Goncalves, 200844 | 30 | II | EGFR | Gefitinib 500 mg daily per os | No objective responses, six (20%) patients experienced stable disease with a median duration of 111.5 days. Median TTP was 37 days and median OS was 107 days. | Gefitinib was well tolerated, the most common drug-related AEs were diarrhea, acne, vomiting, and nausea. No grade 4 events. |
Schilder, 2009 47 | 28 | II | EGFR | Erlotinib 150 mg daily per os | No objective responses with four (16%) achieving stable disease; only one patient had a PFS ≥ 6 months (4%). |
Grade 3 related toxicities included diarrhea, nausea, emesis, dehydration and anorexia. One patient experienced grade 4 renal toxicity. |
Santin, 2011 53 | 38 | II | EGFR | Cetuximab 400 mg/m2 i.v. initial dose followed by 250 mg/m2 weekly | No objective responses with five patients (14.3%) survived without progression for at least 6 months. Median PFS and OS times were 1.97 and 6.7 months, respectively. | Grade 3 adverse events at least possibly related to cetuximab included dermatologic events, GI, anemia, constitutional symptoms, infection, vascular events, pain, and pulmonary, neurological, vomiting and metabolic events. No grade 4 events |
Tinker, 2013 86 | 38 | II | mTor | Temsirolimus (25mg i.v. weekly in 4week cycles), | One patient experienced a partial response (3.0%). 57.6% stable disease. Median PFS: 3.52months. | No toxicity grade 3/4 observed. Adverse effects were mild-moderate in most cases and similar to other temsirolimus studies. |
Coronel, 2011 100 | 36 | III, R | HDAC | Hydralazine and valproate (HV) added to cisplatin topotecan (hydralazine at 182 mg for rapid, or 83 mg for slow acetylators, and valproate at 30 mg/kg, beginning a week before chemotherapy and continued until disease progression) | 4 PRs to CT + HV and 1 in CT + PLA. 29% and 32% stable disease, respectively. Median PFS: 6 months for CT + PLA, 10 months for CT + HV. | Low incidence of grades 3 and 4 toxicity in both arms. G2/3 thrombocytopenia, edema, drowsiness and tremor were statistically higher in CT+HV arm. |
Zhou, 2013 111 | 40 | II, R | Proteasome | rAd-p53 combined with chemotherapy (PCG arm) vs chemotherapy alone (CG arm) | ORR 95% in PCG arm versus 75% for the CG arm. 1-year OS: 90% and 65%, respectively. | Fever was found in 90% of PCG patients (mild to medium grade). No serious adverse events relative to rAd-p53 were observed. |
ORR: Overall response rate; OS: Overall survival; TTP: Time to progression; PFS: Progression free survival; iv: intravenously; R: randomized; GI: gastrointestinal.