Background
PTX is one of the effective agents in the treatment of EC
Authors | Cases (SC/AC/other) | Chemotherapy | Efficacy | ||
---|---|---|---|---|---|
Total | SC | AC | |||
van der Gaast, et al. [20] | 31(NA/NA) | PTX 100–160 mg/m2 iv3h, d1; DDP 60 mg/m2, d1, q2w | 55% | 53% | 60% |
Kelsen, et al. [21] | 37(27/10) | PTX 200 mg/m2, civ24h, d1; DDP 75 mg/m2, d1, q3w | 49% | 60% | 44% |
Polee, et al. [22] | 51(16/31/4) | PTX 180 mg/m2, iv3h, d1; DDP 60 mg/m2, d1, q2w | 43% | 39% | 44% |
Huang, et al. [23] | 30(30/0) | PTX 175 mg/m2, iv3h, d1; DDP 40 mg/ m2, d2, 3, q3w | 59% | 59% | – |
Ilson, et al. [24] | 61(31/30) | PTX 175 mg/m2 iv3h, d1; DDP 20 mg/m2 5d; 5-FU 1 g/m2/d, 5d; q3w | 48% | 50% (CR 20%) | 46%(CR 3%) |
Lin, et al. [25] | 41(41/0) | PTX 35 mg/m2, d1, 4, 8, 11, DDP 20 mg/m2, d2, 5, 9, 12; 5-FU 2 g/m2, q3w | 39% | 39% | – |
Preclinical research shows the radiosensitivity enhancement of PTX
Phase 2 clinical trials of EC patients treated with PTX-based CCR
Authors | Cases (SC/AC/other) | Chemotherapy | Radiation dose (Gy) | Median survival (months) | pCR | ||
---|---|---|---|---|---|---|---|
Total | SC | AC | |||||
Safran, et al. [26] | 41 (12/29) | PTX 60 mg/m2 3 h; DDP 25 mg/m2 d1, 8, 15, 22 | 39.6 | 15 | 29% | 42% | 24% |
Bains, et al. [27] | 41 (16/25) | Induction, DDP 75 mg/m2; PTX 175 mg/m2, W 1, 4; Concurrent, DDP 30 mg/m2/w; PTX 30–80 mg/m2/w, 96 h civ w 7–12 | 50.4 | – | 22% | 31% | 16% |
Urba, et al. [28] | 69 (10/57/2) | DDP 75 mg/m2 d1; PTX 60 mg/m2 d1, 8, 15, 22 | 45 | 24 | 19% | – | – |
Van Meerten, et al. [29] | 54 (12/41/1) | PTX 50 mg/m2, d1, 8, 15, 22, 29; CBP AUC = 2, d1, 8, 15, 22, 29 | 41.4 | – | 25% | – | – |
Meluch, et al. [30] | 129 (35/91/3) | PTX 200 mg/m2, 1 h, d1, 22; CBP AUC = 4, d1, 22; 5-FU 225 mg/m2/d, civ, d1–42 | 45 | 22 | 38% | 53% | 37% |
Lin, et al. [31] | 97 (92/5) | PTX 35 mg/m2, 1 h, d1, d4; DDP 15 mg/m2 d2, d5 | 40 | 29 | 25% | – | – |
Jatoi, et al. [32] | 54 (−/−) | PTX 200 mg/m2, 1 h, d1, 22; CBP AUC = 4, d1, 22; 5-Fu 225 mg/m2/d, civ, d1–42 | 45 | 21.2 | 35% | – | – |
Case-control study of PTX-based regimen versus PF regimen in CCR in EC patients
Institution/ Study Type | Cases | CT | RT | pCR (%) | 3-yr OS (%) | ≥3 Side effect | ||
---|---|---|---|---|---|---|---|---|
Total | SC | AC | ||||||
Cleveland Clinic Foundation [12]/ prospective, non-randomized | 72 | PF | 45 Gy, 1.5 Gy/FX, BID (split course) or 24 Gy postoperative | 27 | 36 | 22 | 36 | Vomiting (1%), mucositis (18%), leucopenia (43%), thrombocytopenia (10%), nephrotoxicity (8%), unplanned hospitalization (25%) |
40 | TP | 23 | 50 | 8 | 30 | Mucositis (13%), leucopenia (95%), neuropathy (13%), unplanned hospitalization (48%) | ||
Duke University [9]/ retrospective | 57 | PF | 45–50.4 Gy, 1.8–2.0 Gy/FX | 40 | – | – | 37 | 24% |
52 | TPF | 39 | – | – | 37 | 34% | ||
Massachusetts General Hospital [33]/ retrospective | 81 | PF | CTV 45 Gy/25FX, GTV 58.5 Gy/25FX (13.5 Gy, 1.5 Gy/FX concomitant boost during the first and second cycles of CT) | 46 | – | – | 39 | 79% |
83 | TPF | 37 | – | – | 42 | 80% |
Rationale for the trial
Methods/design
Design
Objectives
-
3-yr OS◦ Defined in the intent-to-treat population.◦ Time from the start of study treatment (Day 1) to death from any cause.
-
Disease progression-free survival◦ Defined in the intent-to-treat population.◦ Time from Day 1 to the first event of local failure, metastatic recurrence, progression or death.◦ Progression will be examined by computed tomography (CT), esophageal radiography and/or upper endoscopy
-
Local progression-free survival◦ Defined in the intent-to-treat population.◦ Time from Day 1 to the first event of local failure.◦ Local progression will be examined by CT, esophageal radiography and/or upper endoscopy, and is defined as local progression within the irradiated field
-
Number and grade of participants with Adverse Events◦ Adverse events will be graded according to the Common Terminology Criteria for Adverse Events version 4.0 [16]
Patient selection
Initial diagnosis
Inclusion criteria
Exclusion criteria
Study treatment
Chemotherapy
Cisplatin plus 5-fluorouracil regimen (arm a)
Paclitaxel plus 5-fluorouracil regimen (arm B)
Chemotherapy interruption and dose modifications
-
ANC < 1.5 × 109/L
-
Plt < 80 × 109/L
-
≥Grade 3 nonhematological toxicities (nausea, vomiting and alopecia excluded)
Radiotherapy (both arms)
Gross tumor volume (GTV)
Clinical target volume (CTV)
Planning target volume (PTV)
Normal organ contouring and dose restrictions
Dose modifications
Radiotherapy delay
-
WBC < 2.0 × 109/L or ANC < 1.0 × 109/L
-
Plt < 50 × 109/L
-
Grade 3 or higher non-hematological toxicity