1. Chemotherapy regimens.
| Study ID | Common treatment | Intervention 1 | Intervention 2 |
| Anderson 1983 | C: 1.2 g/m2 IV on day 1; O: 2.0 mg/m2 (max 2 mg) IV on days 3,10,17 and 24; MTX: 6.25 mg/m2 IT on days 5, 31, and 34; P: 15 mg/m2 (max 60 mg) orally qds on days 3 to 30 decreasing to zero on days 31 to 33. Radiation therapy. Tumour excision attempted in patients with localised disease. Laparotomy and biopsy in patients with non‐localised disease. | COMP
Induction: MTX 300 mg/m2 IV on day 12. Maintenance: C: 1 g/m2 IV on day 1; O: 1.5 mg/m2 IV on days 1 and 4; MTX: 6.25 mg/m2 IT on day 1 (excluded from 1st maintenance cycle), then 300 mg/m2 IV on day 15. Repeat maintenance cycle every 28 days. |
LSA2 L2 (modified).
Induction: DAU; 60 mg/m2 IV on days 12 and 13. Consolidation: CYT; 100 mg/m2 IV 5 days on, 2 days off x 2 weeks; THIO; 50 mg/m2 orally 8 to 12 hrs post CYT injection; ASP; 6000 IU/m2 IM daily x 14 days post CYT and THIO; MTX; 6.25 mg/m2 IT x2 doses 3 days apart, 2 to 3 days after last dose of ASP; CAR; 60 mg/m2 IV single dose given 2 to 3 days after completion of MTX. Maintenance: THIO: 300 mg/m2 orally on days 1 to 4, 600 mg/m2 IV on day 5; H: 2.4 g/m2 orally on days 1 to 4; DAU: 45 mg/m2 orally on day 5,;CYT: 150 mg/m2 IV days 1 to 5; O: 2.0 mg/m2 (max 2 mg) IV on day 5; MTX: 6.25 mg/m2 IT x 2 doses 3 days apart. Repeat maintenance cycles 1 to 5. |
| Brecher 1997 | None. | A
Prespecified duration:
Induction: C: on day 1 (dose not specified); MTX: on days 24 and 31 (dose not specified); O: weekly (x 5 weeks dose not specified); P: daily x 4 weeks (dose not specified). Consolidation (22 weeks): C: days 52 and 102; MTX: on days 74,81,124, and 131; O: I hour prior to each MTX. Maintenance: (11 weeks): O and MTX on days 174 and 216. CNS prophylaxis: Ara‐C, MTX and H. |
B
Duration determined by clinical response. Induction: fractionated C,O and DOX. Infusion phase: sequential continuous infusion of MTX and Ara‐C (pending mucosal and bone marrow recovery). Repeat induction and infusion x 4 with dose of Ara‐C being doubled with each course. CNS prophylaxis: MTX and Ara‐C. |
| Cairo 2003 | Prephase: C: 0.3 g/m2 IV; O: 1 mg/m2 IV on day1; P: 60 mg/m2 IV or orally in 2 fractions on days 1 to 7; MTX+HYD+Ara‐C: 30 mg IT on days 1,3 and 5. Induction: COPADM 1 (started 1 week after day 1 of prephase). O: 2 mg/m2 (max 2 mg) IV;high‐dose MTX: 8 g/m2 IV x 4 hours on day1; CFR: 15 mg/m2 every 6 hours orally on days 2 to 4; MTX+HYD+Ara‐C: 30 mg IT on day 2,4 and 6; DOX: 60 mg/m2 IV on day 2; C: 0.5 g/m2 IV (in 2 fractions) on days 2 to 4; P: 60 mg/m2 IV or orally on days 1 to 6. COPADM 2 similar to COPADM1 except for: 2nd O dose: 2 mg/m2 (max 2 mg) IV on day 6; C: 1 g/m2 IV (in 2 fractions) on days 2 to 4. |
Reduced intensity Similar to standard dose except for consolidation drugs are given at 2/3 the standard doses and deletion of M2 to 4 maintenance. | Standard dose
Consolidation: (x 2 courses).
Ara‐C: 50 mg/m2 CI x 12 hours on days 1 to 5 (8 pm to 8 am); high‐dose Ara‐C 3 g/m2 IV x 3 hours on days 2 to 5 (8 am to 11 am); VP‐16: 200 mg/m2 IV on days 2 to 5 (2 pm to 4 pm). Maintenance (monthly alternating courses). M1: O: 2 mg/m2 (max 2 mg) IV; high‐dose MTX: 8 g/m2 IV x 4 hours on day 1; CFR: 15 mg/m2 every 6 hours orally on days 2 to 4; P: 60 mg/m2 orally on days 1 to 5; MTX+HYD+Ara‐C: 30 mg IT on day 2; C: 0.5 g/m2 IV on days 1 and 2; DOX: 60 mg/m2 IV on day 2. M2/M4: VP‐16: 150 mg/m2 IV on days 1 to 3; Ara‐C: 100 mg/m2 SC (in 2 fractions) on days 1 to 5. M3: similar to M1 but without high‐dose MTX and IT. |
| Magrath 1973 | IV C 40 mg/kg x 2 doses 2 weeks apart. | Lomustine (70 mg/m2) administered orally. | No treatment. |
| Magrath 1976 | IV C 40 mg/kg x 2 doses (a third dose was given when complete remission was not achieved with the standard 2 doses). | 0.5 ml of freshly constituted BCG suspension administered by scarification. | No treatment. |
| Olweny 1976 | None. | C: 40 mg/kg IV on day 1,repeated after 2 weeks or as soon as toxicity is abated. | C: 30 mg/kg IV on day 1; O: 2 mg/m2 IV on day 1; MTX: 15 mg/m2 orally on days 1 to 3. This is repeated 12 to 14 days later. |
| Patte 1991 | Reduction phase: C: 0.3 g/m2 IV; O: 1 mg/m2 IV on day 1; P: 2 mg/kg orally on days 1 to 7; MTX+HYD: 15 mg/m2 IT on day 1. Induction: COPADM 1 (started 1 week after day 1 of prephase). O: 2 mg/m2 IV;high‐dose MTX: 3 g/m2 IV x 3 hours on day 1; CFR: 15 mg/m2 every 6 hours orally on days 2 to 4; MTX+HYD: 15 mg IT on days 2 and 6; DOX: 60 mg/m2 IV on day 2; C: 0.5 g/m2 IV (in 2 fractions) on days 2 to; P: 2 mg/kg IV or orally on days 1 to 6. COPADM 2 similar to COPADM 1 except for: addition of 2nd O dose: 2 mg/m2 IV on day 6; C: 1 g/m2 IV (in 2 fractions) on days 2 to 4. CYM: high‐dose MTX 3 g/m2 IV x 3 hours on day 1; CFR: 15 mg/m2 every 6 hrs orally on days 2 to 4; Ara‐C: 100 mg/m2 CI on days 2 to 6; Ara‐C+HYD: 30 mg/m2 IT on day 6. Maintenance (monthly alternating courses) M1: O: 2 mg/m2 IV; high‐dose MTX 3 g/m2 IV x 3hours on day 1; CFR: 15 mg every 6 hours orally on days 2 to 4; P: 2 mg/kg orally on days 1 to 5; MTX+HYD: 15 mg IT on day 2; C: 0.5 g/m2 IV on days 1 and 2; DOX: 60 mg/m2 IV on day 2. M2: Lomustine: 60 mg/m2 orally on day 28,; Ara‐C: 100 mg/m2 SC (in 2 fractions) on days 28 to 31; Ara‐C+HYD: 30 mg/m2 IT on day 28; THIO: 150 mg/m2 orally on days 28 to 31. |
Long arm: CYM 1, Mini‐BACT: Lomustine: 60 mg/m2 orally on day 1; Ara‐C: 100 mg/m2 CI on days 2 to 6; THIO: 150 mg/m2 orally on days 2 to 6; C: 0.5 g/m2 IV on days 2 to 4. M1, M2, M1, M2. | Short arm: CYM 1 and 2, M1. |
| Patte 2007 | Prephase COP + IT MTX. Maintenance: O, P, AD, high‐dose MTX given if 20% response at day 7 after COP. Leucovorin rescue treatment. NB. There is a second stage which involves subgroup of main interventions to receive either M1 (C1g/m2, O, P, AD, high‐dose MTX, or not. |
1A: COPADM1: (Cyclophosphamide 1.5mg/m2) on days 2 and 6; CYM: (CYT IV on days 2 to 6 and IT CYT on day 6): M1 C 1g/m2, O, P, AD, high‐dose MTX. | 1B: COPADM2 (double dose of C is given, O, P, AD. high‐dose MTX) on days 2 and 6, CYM (CYT IV on days 2 to 6 and IT CYT on day 6). |
| Sullivan 1991 | Induction: C: 1.2 g/m2 IV on day 1, repeat on day 1 of weeks 7 and 14; O: 2.0 mg/m2 (max 2.0mg) IV on days 2 or 3 weekly x 4 then 1.0 mg/m2 IV given 1 hour before MTX infusion; P: 60 mg/m2 (max 60 mg) orally daily from day 1 x 28 days; MTX: 2 6‐hour infusion starting from week 3, starting dose 50 mg/kg increasing to 100 mg/kg then to 200 mg/kg throughout the rest of the treatment, given as 2 doses every 7 weeks during induction and consolidation and every 6 weeks during maintenance; CFR: 15 mg IV 3 hourly x 9 doses then 15 mg 6 hourly x 8 doses after each MTX infusion. CNS prophylaxis: CYT: 45 mg/m2 on D1 and 2, MTX 15 mg/m2 on day 3 starting on day 2 of induction, subsequently given as triple therapy (CYT 60 mg/m2, MTX 15 mg/m2 (max 15 mg, HYD 30 mg/m2) at week 6 and 14, then 24 hours before each pair of MTX infusions. Maintenance: triple therapy, IV MTX, IV O. |
Maintenance regimen for 2 months. | Maintenance regimen for 6 months. |
| Ziegler 1971 | Unclear.unclear | MTX 25 mg/m2 IT alternating with Ara‐C 50 mg /m2 IT every 4 days. Two doses of each drug were given. | No intrathecal therapy. |
| Ziegler 1972a | None. | C: 40 mg/kg IV at 2‐weekly intervals for 6 doses. | TRIKE schedule C: 40 mg/kg followed in two weeks by O: 1.4 mg/m2 IV on day 1 and MTX 15 mg/m2 orally on days 1 to 4; Ara‐C: two weeks later; 250 mg/m2 CI daily x 3 days. |
AD: adriamycin (doxorubicin) Ara‐C: cytosine arabinoside ASP: asparaginase BCG: Bacille‐Calmette‐Guerin C: cyclophosphamide CAR: carmustine CFR: citrovorum factor rescue CI: continuous infusion CNS: central nervous system COMP: cyclophosphamide, oncovin, methotrexate and prednisolone COP: cyclophosphamide, oncovin and prednisolone CYM: CYT plus high‐dose MTX CYT: cytarabine DAU: daunorubicin DOX: doxorubicon H: hydroxyurea HYD: hydrocortisone IM: intramuscular IT: intrathecal IV: intravenous MTX: methotrexate O: oncovin (vincristine) P: prednisolone qds: four times daily THIO: thioguanine