Table 2.
Description of the treatment in the VAI group (N = 243).
| < 12 years old N = 64 | 12-17 years old N = 100 | 18-24 years old N = 42 | ≥ 25 years old N = 37 | p(1) | |
|---|---|---|---|---|---|
| Total number of maintenance courses administered (MD=4) | 0.0005(2) | ||||
| 7 and fewer | 5 (8 %) | 8 (8 %) | 11 (26 %) | 10 (28 %) | |
| 8 | 54 (87 %) | 84 (84 %) | 29 (69 %) | 25 (69 %) | |
| 9 and more | 3 (5 %) | 7 (7 %) | 2 (6 %) | 1 (3 %) | |
| Courses of VAI administered (MD=3) | 0.05 | ||||
| 7 and fewer | 17 (27 %) | 18 (18 %) | 15 (36 %) | 12 (33 %) | |
| 8 and more | 46 (72 %) | 81(81 %) | 27 (64 %) | 24 (67 %) | |
| Courses of VAC administered (MD=3) | 0.37 | ||||
| No | 53 (84 %) | 90 (91 %) | 38 (90 %) | 34 (94 %) | |
| Yes (one or more) | 10 (16 %) | 9 (9 %) | 4 (9 %) | 2 (6 %) | |
| Courses other than VAI/VAC (MD=5)(3) | 0.36 | ||||
| No | 58 (94 %) | 91 (92 %) | 39 (95 %) | 36 (100 %) | |
| Yes (one or more) | 4 (6 %) | 8 (8 %) | 2 (5 %) | 0 | |
| Time interval between 1stVAI1 and 8thVAI (weeks) (MD=2) | 0.009 | ||||
| Median (range) | 25 (6; 44) | 26 (10; 38) | 24 (6; 45) | 24 (6; 37) | |
| Cumulative dose of equivalent-Ifosfamide VAI1-VAI8 (g/m²)(4) (MD=2) | 0.17 | ||||
| Median | 46.6 | 47.1 | 45.8 | 45.2 | |
| Range | (6.0; 52.5) | (12.1; 49.6) | (11.6; 48.2) | (9.3; 49.1) | |
| Relative Dose intensity of alkylating agents in maintenance courses (%)(5) (MD=3) | 0.39 | ||||
| Median (range) | 89 (7; 109) | 90 (56; 107) | 93 (41; 105) | 92 (27; 104) | |
| RDI<80 % (MD=3) | 0.64 | ||||
| No | 52 (83 %) | 75 (77 %) | 31 (74 %) | 30 (81 %) | |
| Yes | 11 (17 %) | 23 (23 %) | 11 (26 %) | 7 (19 %) | |
| Reported reason for treatment modification (MD = 18) | |||||
| Toxicity | 4 | 8 | 4 | 7 | |
| Progression | 0 | 3 | 0 | 0 | |
| Patient’s choice | 0 | 1 | 1 | 0 | |
| Physician’s choice | 0 | 1 | 1 | 0 | |
| Other | 0 | 3 | 1 | 0 | |
| Reason for early stop of treatment | |||||
| Toxicity | 0 | 0 | 1 | 0 | |
| Progression | 5 | 5 | 4 | 5 | |
| Patient’s choice | 0 | 0 | 1 | 2 | |
| Physician's choice | 0 | 1 | 5 | 2 | |
| Unknown reason | 0 | 2 | 1 | 1 |
MD, missing data; RDI: Relative Dose Intensity; VAI: Vincristine-Dactinomycin-Ifosfamide; VAC: Vincristine-Dactinomycin-Cyclophosphamide.
(1) P-value of the test comparing < 12 years versus 12-17 years old versus ≥ 18 years (pooling the two groups of patients ≥ 18 years because of the limited number of patients)
(2) P-value of the test comparing ≤ 7 versus ≥ 8 maintenance courses
(3) The courses other VAI/VAC consisted in dactinomycin alone in all but three courses, 1 course of vincristine + dactinomycin, 1 course of vincristine + ifosfamide, and 1 course of dactinomycin + ifosfamide
(4) The cumulative dose of equivalent-Ifosfamide was computed from the 1st to the 8th course (or less if treatment permanently discontinued before the 8th course), considering dose of ifosfamide or cyclophosphamide, assuming that 1.5 g/m² of cyclophosphamide was equivalent to 6 g/m² of ifosfamide, as assumed when comparing ifosfamide to cyclophosphamide in standard risk patients (Euro-E.W.I.N.G-99 R1 trial 21). Consequently, cumulative dose = cumulative dose of ifosfamide (g/m²) + 4 x cumulative dose of cyclophosphamide (g/m²)
(5) The dose intensity (DI) of alkylating agent was computed as the cumulative dose of alkylating agents over the first eight maintenance courses (or less if treatment permanently discontinued before the 8th course) divided by the corresponding treatment duration (including 20 days after the last course). The relative dose-intensity of alkylating agents (RDI) was finally computed as the ratio between the observed DI and the theoretical dose intensity (6 g/m² every 3 weeks, equivalent to 2 g/m²/week).