Table 1.

Preliminary results of clinical trials of targeted agents in cervical cancer.

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.