Table 1: Phases I and II studies on intravenous dose-dense paclitaxel.

Study Regimen (#)PI (m) RR (%)CR () Median PFS (m) Median  
OS  
(m)
Adverse effectsComments
Paclitaxel  
dose (mg/m2)
Carboplatin dose (mg/m2)

Phase I: single agent
Lofflerr et al., 1996 [11]40–90/week  
1-hour infusion for 6 weeks
50405NANA(i) Hematologic toxicity-mild  
(ii) No grade 3 or 4 haematological toxicity, neurological or cardiotoxicity up to 90 mg/m2/wk.  
(iii) No hypersensitivity reactions (patients received premedication).
(i) 100% prior chemotherapy.  
(ii) Median dose intensity was 410 mg/m2/6 wk (range, 200 to 540 mg/m2/6 wk).
Fennelly et al., 1997 [12]40–100/week1830NANANA(i) No mucositis or grade III neuropathy was seen.  
(ii) Alopecia occurred in one.
(i) 100% prior chemotherapy (2–5 prior regimens).  
(ii) Partial responses were seen in four of 13 assessable patients (30%).  
(iii) Dose-limiting toxicity was reached at 100 mg/m2.  
(iv) 2-3 patients experience treatment delay.  
(v) Maximum-tolerated dose of 80 mg/m2.
Abu-Rustum et al., 1997 [13]60–100 over 1 hour/week4528.9NANANA(i) No patient had febrile neutropenia.(i) 100% prior chemotherapy (1–8 prior regimens).

Phase II: Single agent
Markman et al., 2001 [14]80 over 1 hour/week53 (52)25NANANATherapy discontinued in 
(i) 4 patients who had peripheral neuropathy, 
(ii) 1 patient due to painful fingernail beds.
(i) 100% platinum and paclitaxel resistant.
(ii) Therapy was discontinued in 5 patients because of toxicity.  
(iii) Only 13 (1%) were modified (dose reduction or treatment delay) because of side effects.

Phase II: Combined with platinum agent
Kikuchi et al., 2005 [15]80 over 1 hour/weekAUC 2/week27>6 81848.3NA(i) Neutropenia (1.7%), thrombocytopenia (5.1%).  
(ii) No cases of peripheral neuropathy (grades 3 and 4) in weekly combined T-C.
Cadron et al., 2007 [16]90 over 1 hour/weekAUC 4/week24 
9
>6 
≤6
73 
38
NR  
8
10.5  
6.75
(i) Grade 3/4 neutropenia (34%) and neutropenic fever in 2%.  
(ii) Nausea and vomiting and fatigue were the most frequent nonhematological side effects.
(i) Dose reduction was necessary in 25% of patients.
Pignata et al., 2008 [17]60 over 1 hour/weekAUC 2/week24 (13)1st line38.5232.013.6(i) No toxic death was recorded.  
(ii) Grade 2 anaemia was reported in seven patients (27%).  
(iii) No febrile neutropenia was observed.  
(iv) Grade 3 and 4 neutropenia was recorded in five (19%) and one (4%) patients.
(v) Grade 3 thrombocytopenia occurred in one patient (4%).
Safra et al., 2014 [18]80 over 1 hour/weekAUC 2/week1331st line86.464.527.4(i) Higher anaemia (grade III + IV: 6.8% vs. 5.3%) + IV neutropenia (14.4% vs. 6.9%) decreased grade II alopecia (23.5% vs. 98.1%) and thrombocytopenia (grade III + IV: 0 vs. 2.3%).
Havrilesky et al., 2003 [19]80 over 1 hour/weekAUC 2/week D1, D8, D15 until progression/CR + 8 courses 29  
21 
8
Total group 
>6 
<6
83 
100 
38
16 
15 
1
11.411.5 
13.7 
3.2
(i) Hematologic toxicity was common (grade 3 neutropenia 32%, no grade 4 neutropenia, grade 3 or 4 thrombocytopenia 14.2%). (i) Toxicity managed by treatment delay, dose reduction of paclitaxel, or discontinuation of carboplatin.
van der Burg et al., 2014 [20]90 over 1 hour/weekAUC 4/week D1, D8 D15 D29 D36 D49 + 6x TC q3w 108 
65 
43
Total group 
>6 
<6
76 
58
16 
42
26 
15
8 
13
(i) Neutropenia 30%, thrombocytopenia 8%, febrile neutropenia 0.5%.  
(ii) Nonhaematologic toxicity was low.
(i) Treatment was delayed in 16%, and dose reduced in 2% of cycles.

: number of patients, #: assessable for response, m: months, PI: platinum treatment free interval, RR: response rate, CR: complete remission, T: paclitaxel, C: carboplatin, PFS: progression free survival, OS: overall survival, NA: not available in paper or abstract, and NR: not yet reached.
Elderly population, patient aged ≥70 years.