Background
Methods
Patient selection
Treatment
Statistical methods
Results
Patient characteristics
Number of patients (%) | ||||
---|---|---|---|---|
Patients' characteristics | DD/DI arm (N = 86) | HDI arm (N = 80) | ||
Age, years
| ||||
Mean (SD)
| 47 (13) | 52 (13) | ||
Gender
| ||||
Male
| 47 | (55) | 54 | (67) |
Female
| 39 | (45) | 26 | (33) |
ECOG Performance Status
| ||||
0
| 81 | (94) | 76 | (95) |
1
| 5 | (6) | 4 | (5) |
Site of primary tumor
| ||||
Head/neck
| 3 | (3) | 6 | (7) |
Trunk
| 50 | (58) | 40 | (50) |
Upper limb
| 7 | (8) | 6 | (8) |
Lower limb
| 26 | (30) | 24 | (30) |
Unknown
| 0 | (0) | 4 | (5) |
Ulceration
| ||||
No
| 45 | (52) | 36 | (45) |
Yes
| 33 | (39) | 34 | (43) |
Unknown
| 8 | (9) | 10 | (12) |
Breslow's thickness (mm)
| ||||
≤ 1
| 2 | (2) | 7 | (9) |
1.01 – 2.0
| 27 | (31) | 18 | (23) |
2.01 – 4.0
| 30 | (35) | 29 | (36) |
>4
| 22 | (26) | 17 | (21) |
Unknown
| 5 | (6) | 9 | (11) |
Nodal classification
| ||||
N0
| 0 | (0) | 2 | (2) |
N1
| 56 | (65) | 46 | (58) |
N2
| 19 | (22) | 24 | (30) |
N3
| 11 | (13) | 8 | (10) |
Toxicity evaluation
Number of patients (%) | ||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
DD/DI arm (N = 86) | HDI arm (N = 80) | |||||||||||||||
Event |
Grade 1
|
Grade 2
|
Grade 3
|
Grade 4
|
Grade 1
|
Grade 2
|
Grade 3
|
Grade 4
| ||||||||
Flu-like symptoms
| ||||||||||||||||
Fatigue
| 19 | (22) | 26 | (30) | 25 | (29) | 0 | 14 | (17) | 27 | (34) | 19 | (24) | 3 | (4) | |
Fever
| 28 | (33) | 33 | (38) | 7 | (8) | 0 | 25 | (31) | 23 | (29) | 8 | (10) | 1 | (1) | |
Rigors/chills
| 15 | (17) | 5 | (6) | 0 | 0 | 12 | (15) | 3 | (4) | 3 | (4) | 0 | |||
Arthralgia/myalgia
| 26 | (30) | 17 | (20) | 1 | (1) | 0 | 29 | (36) | 12 | (15) | 3 | (4) | 1 | (1) | |
Sweating
| 8 | (9) | 3 | (3) | 0 | 0 | 8 | (10) | 1 | (1) | 1 | (1) | 0 | |||
Gastrointestinal
| ||||||||||||||||
Nausea/vomiting
| 32 | (37) | 12 | (14) | 2 | (2) | 0 | 27 | (34) | 12 | (15) | 1 | (1) | 0 | ||
Constipation
| 13 | (15) | 5 | (6) | 0 | 0 | 9 | (11) | 3 | (4) | 0 | 0 | ||||
Diarrhea
| 11 | (13) | 1 | (1) | 0 | 0 | 5 | (6) | 1 | (1) | 1 | (1) | 1 | (1) | ||
Anorexia
| 30 | (35) | 10 | (12) | 3 | (3) | 0 | 14 | (17) | 12 | (15) | 6 | (7) | 0 | ||
Hematological
| ||||||||||||||||
Leukopenia
| 13 | (15) | 32 | (37) | 21 | (24) | 0 | 28 | (35) | 25 | (31) | 7 | (9) | 0 | ||
Anemia
| 12 | (14) | 0 | 1 | (1) | 0 | 16 | (20) | 3 | (4) | 0 | 0 | ||||
Granulocytopenia
| 7 | (8) | 21 | (24) | 31 | (36) | 7 | (8) | 13 | (16) | 23 | (29) | 21 | (26) | 2 | (2) |
Platelets
| 11 | (13) | 1 | (1) | 3 | (3) | 1 | (1) | 16 | (20) | 5 | (6) | 0 | 0 | ||
Hemorrhage
| 2 | (2) | 4 | (5) | 0 | 0 | 1 | (1) | 1 | (1) | 0 | 0 | ||||
Hepatic function
| ||||||||||||||||
Bilirubin
| 3 | (3) | 2 | (2) | 0 | 0 | 6 | (7) | 0 | 0 | 0 | |||||
SGOT/SGPT
| 16 | (19) | 11 | (13) | 18 | (21) | 15 | (17) | 21 | (26) | 24 | (30) | 18 | (22) | 3 | (4) |
Alkaline phosphatase
| 8 | (9) | 2 | (2) | 0 | 0 | 8 | (10) | 3 | (4) | 0 | 0 | ||||
Liver dysfunction
| 0 | 2 | (2) | 1 | (1) | 0 | 3 | (4) | 1 | (1) | 1 | (1) | 0 | |||
Neurologic
| ||||||||||||||||
Depression/anxiety
| 19 | (22) | 14 | (16) | 7 | (8) | 0 | 20 | (25) | 12 | (15) | 12 | (15) | 1 | (1) | |
Cognitive disturbance
| 10 | (12) | 10 | (12) | 4 | (5) | 0 | 10 | (12) | 7 | (9) | 2 | (2) | 0 | ||
Cardiovascular
| ||||||||||||||||
Hypertension
| 6 | (7) | 1 | (1) | 0 | 0 | 2 | (2) | 1 | (1) | 2 | (2) | 0 | |||
Hypotension
| 1 | (1) | 1 | (1) | 0 | 0 | 5 | (6) | 4 | (5) | 0 | 0 | ||||
Ritmo
| 0 | 2 | (2) | 0 | 0 | 1 | (1) | 1 | (1) | 0 | 0 | |||||
Cardiac dysfunction
| 6 | (7) | 4 | (5) | 0 | 0 | 7 | (9) | 6 | (7) | 2 | (2) | 1 | (1) | ||
Pulmonary
| ||||||||||||||||
Dyspnea
| 8 | (9) | 3 | (3) | 0 | 0 | 13 | (16) | 4 | (5) | 0 | 0 | ||||
Cough
| 7 | (8) | 1 | (1) | 0 | 0 | 13 | (16) | 1 | (1) | 0 | 0 | ||||
Dermatology
| ||||||||||||||||
Skin
| 15 | (17) | 7 | (8) | 4 | (5) | 0 | 15 | (19) | 11 | (14) | 2 | (2) | 1 | (1) | |
Local
| 1 | (1) | 0 | 1 | (1) | 0 | 5 | (6) | 1 | (1) | 1 | (1) | 0 | |||
Metabolic
| ||||||||||||||||
Hyperglycaemia
| 7 | (8) | 3 | (3) | 3 | (3) | 0 | 5 | (6) | 3 | (4) | 0 | 0 | |||
Hypoglycaemia
| 1 | (1) | 2 | (2) | 4 | (5) | 2 | (2) | 1 | (1) | 3 | (4) | 0 | 1 | (1) |
Delivered treatment and dose intensity
Number of cycles (%) | ||||
---|---|---|---|---|
DD/DI arm | HDI arm | |||
N° cycles delivered | 272 | 701 | ||
According to protocol | 72 | (26) | 187 | (27) |
Modified in dose less than 20% | 64 | (23) | 176 | (25) |
Modified in dose more than 20% | 136 | (50) | 338 | (48) |
Number of patients (%) | ||||
---|---|---|---|---|
DD/DI arm (N = 86) | HDI arm(N = 80) | |||
Completed therapy | 54 | (63) | 32 | (40) |
Reasons for discontinuation | ||||
Toxicity
| 11 | (13) | 14 | (17) |
Refusal
| 11 | (13) | 15 | (19) |
Disease Progression
| 10 | (12) | 19 | (24) |
Number of patients (%) | ||||
---|---|---|---|---|
Time from randomization | DD/DI arm (N = 86) | HDI arm(N = 80) | ||
Induction | 56 | (65) | 52 | (65) |
3 months | 35 | (49) | 42 | (64) |
5 months | 25 | (42) | 33 | (55) |
7 months | 20 | (36) | 23 | (43) |
DD/DI arm (N = 86) | HDI arm (N = 80) | |||
---|---|---|---|---|
Mean (SD) | Median (Range) | Mean (SD) | Median (Range) | |
Target dose (MU/m2) | 1600 | 1840 | ||
MU/m2 received | 974.6 (455.6) | 1034.4 (40 -1620.2) | 1052.2 (509.2) | 1155.9 (20-1888.9) |
Target DI* MU/m2/week | 50 | 35.4 | ||
Actual DI MU/m2/week | 37.1 (10.8) | 36.4 (5–52.1) | 34.1 (14.4) | 30.7 (5–91.8) |
% of target DI | 0.74 (0.2) | 0.73 (0.1–1.0) | 0.96 (0.4) | 0.87 (0.1–2.6) |
Supportive therapy
Number of patients (%) | ||||
---|---|---|---|---|
Cycle 1 (intravenously) | DD/DI arm (N = 86) | HDI arm (N = 80) | ||
Paracetamol | 79 | (92) | 71 | (89) |
Anti-emetics | 47 | (55) | 44 | (55) |
Anti-diarrhea | 3 | (3) | 2 | (2) |
Anti-anxiety | 20 | (23) | 15 | (19) |
Vitamin | 22 | (26) | 15 | (19) |
Subsequent cycles
|
DD/DI arm (N = 71)
|
HDI arm (N = 69)
| ||
Paracetamol | 64 | (90) | 55 | (80) |
Anti-emetics | 44 | (62) | 21 | (30) |
Anti-diarrhea | 6 | (8) | 2 | (3) |
Anti-anxiety | 19 | (27) | 16 | (23) |
Vitamin | 21 | (30) | 18 | (26) |