Treatment details of total therapy 1 and total therapy 2
Regimen . | Regimen details . |
|---|---|
| Total Therapy 1 | |
| Induction phase | |
| Cycles 1-3, VAD | Vincristine (0.5 mg/d × 4 d) CI; Adriamycin (10 mg/m2/d × 4 d) CI; Dexamethasone 40 mg PO d 1-4, 9-12, 17-20 |
| Cycle 4, HD-CTX | Cyclophosphamide (6 g/m2 in 5 divided doses, 1.2 g/m2 every 3 h) + Mesna (3.6 g/m2); GM-CSF 250 μg/m2/d → PBSC collection |
| Cycle 5, EDAP | Etoposide (100 mg/m2/d × 4 d) CI; cis-Platin (25 mg/m2/d × 4 d)Arabinosyl-cytosine (1 g/m2 d 5); Dexamethasone 40 mg d 1-5; GM-CSF 250 μg/m2/d |
| Transplantation phase | |
| First transplantation | Melphalan (100 mg/m2 on d -3 and -2); PBSC d 0; GM-CSF 250 μg/m2/d |
| Second transplantation | Melphalan (100 mg/m2 on d -3 and -2); PBSC d 0; GM-CSF 250 μg/m2/d; (In case of < PR: melphalan 140 mg/m2 plus total body irradiation 8.5 Gy in 5 equal fractions of 1.7 Gy every 12 h) |
| Maintenance phase | |
| Interferon | 3 million U/m2 SQ 3 × wk until relapse |
| Total therapy 2 | |
| Induction | |
| Cycle 1, VAD | Vincristine (0.5 mg/d × 4 d) CI; Adriamycin (10 mg/m2/d × 4 d) CI; Dexamethasone 40 mg PO d 1-4, 9-12, 17-20 |
| Cycle 2, DCEP | Cyclophosphamide (400 mg/m2/day × 4 d) CI; Etoposide (40 mg/m2/day × 4 d) CI; cis-Platin (10 mg/m2/day × 4 d) CI; Dexamethasone (40 mg/d) PO days 1-4 |
| Cycle 3, CAD | Cyclophosphamide (750 mg/m2/day × 4 d) CI; Adriamycin (15 mg/m2/d × 4 d) CI; G-CSF 10 μg/kg SQ twice daily → PBSC collection |
| Cycle 4, DCEP | Cyclophosphamide (400 mg/m2/day × 4 d) CI; Etoposide (40 mg/m2/day × 4 d) CI; cis-Platin (10 mg/m2/day × 4 d) CI; Dexamethasone (40 mg/d) PO days 1-4 |
| Transplantation | |
| First transplantation | Melphalan 200 mg/m2 d -1 (reduce to 140 mg/m2 for age >70 years or creatinine >3 mg/dL) |
| Second transplantation | Melphalan 200 mg/m2 d -1 (reduced to 140 mg/m2 for age >70 years or creatinine >3 mg/dL) < PR: BCNU 300 mg/m2 d -5; Etoposide 200 mg/m2; Arabinosyl cytosine 400 mg/m2 d -5 through -2; Melphalan 140 mg/m2 d -2 |
| Consolidation | |
| Randomized arm A: DCEP | Dexamethasone 40 mg/d PO d 1-4; cyclophosphamide (300 mg/m2/d × 4 d) CI; etoposide (30 mg/m2/d × 4 d) CI; cis-platin (7.5 mg/m2/d × 4 d) CI every 3 months for 4 cycles |
| Randomized arm B | |
| DCEP* | Dexamethasone 40 mg/d PO d 1-4; cyclophosphamide (300 mg/m2/d × 4 d) CI; etoposide (30 mg/m2/d × 4 d) CI; cis-platin (75 mg/m2/d × 4 d) |
| CAD* | Cyclophosphamide (400 mg/m2/d × 4 d) CI; adriamycin (10 mg/m2/d × 4 d) CI; dexamethasone 40 mg/d PO d 1-4 |
| DPACE | Dexamethasone 40 mg/d PO d 1-4; cis-platin (75 mg/m2/d × 4 d) CI; adriamycin (10 mg/m2/d × 4 d) CI; cyclophosphamide (300 mg/m2/d × 4 d) CI; etoposide (30 mg/m2/d × 4 d) CI; every 3 months for 4 cycles. |
| DEX | In case of failure to recover platelets to at least 100 000/μL or failure to achieve >25% M-protein reduction with first cycle of DCEP in induction: DEX 40 mg d 1-4 every 28 d for 1 year. |
| Maintenance | |
| Interferon | 3 million U/m2 SQ 3 × wk plus first year of maintenance: Dexamethasone 40 mg every 3 months on d 1-4, 9-12, 17-20 |
| Second year onward; interferon alone |
Regimen . | Regimen details . |
|---|---|
| Total Therapy 1 | |
| Induction phase | |
| Cycles 1-3, VAD | Vincristine (0.5 mg/d × 4 d) CI; Adriamycin (10 mg/m2/d × 4 d) CI; Dexamethasone 40 mg PO d 1-4, 9-12, 17-20 |
| Cycle 4, HD-CTX | Cyclophosphamide (6 g/m2 in 5 divided doses, 1.2 g/m2 every 3 h) + Mesna (3.6 g/m2); GM-CSF 250 μg/m2/d → PBSC collection |
| Cycle 5, EDAP | Etoposide (100 mg/m2/d × 4 d) CI; cis-Platin (25 mg/m2/d × 4 d)Arabinosyl-cytosine (1 g/m2 d 5); Dexamethasone 40 mg d 1-5; GM-CSF 250 μg/m2/d |
| Transplantation phase | |
| First transplantation | Melphalan (100 mg/m2 on d -3 and -2); PBSC d 0; GM-CSF 250 μg/m2/d |
| Second transplantation | Melphalan (100 mg/m2 on d -3 and -2); PBSC d 0; GM-CSF 250 μg/m2/d; (In case of < PR: melphalan 140 mg/m2 plus total body irradiation 8.5 Gy in 5 equal fractions of 1.7 Gy every 12 h) |
| Maintenance phase | |
| Interferon | 3 million U/m2 SQ 3 × wk until relapse |
| Total therapy 2 | |
| Induction | |
| Cycle 1, VAD | Vincristine (0.5 mg/d × 4 d) CI; Adriamycin (10 mg/m2/d × 4 d) CI; Dexamethasone 40 mg PO d 1-4, 9-12, 17-20 |
| Cycle 2, DCEP | Cyclophosphamide (400 mg/m2/day × 4 d) CI; Etoposide (40 mg/m2/day × 4 d) CI; cis-Platin (10 mg/m2/day × 4 d) CI; Dexamethasone (40 mg/d) PO days 1-4 |
| Cycle 3, CAD | Cyclophosphamide (750 mg/m2/day × 4 d) CI; Adriamycin (15 mg/m2/d × 4 d) CI; G-CSF 10 μg/kg SQ twice daily → PBSC collection |
| Cycle 4, DCEP | Cyclophosphamide (400 mg/m2/day × 4 d) CI; Etoposide (40 mg/m2/day × 4 d) CI; cis-Platin (10 mg/m2/day × 4 d) CI; Dexamethasone (40 mg/d) PO days 1-4 |
| Transplantation | |
| First transplantation | Melphalan 200 mg/m2 d -1 (reduce to 140 mg/m2 for age >70 years or creatinine >3 mg/dL) |
| Second transplantation | Melphalan 200 mg/m2 d -1 (reduced to 140 mg/m2 for age >70 years or creatinine >3 mg/dL) < PR: BCNU 300 mg/m2 d -5; Etoposide 200 mg/m2; Arabinosyl cytosine 400 mg/m2 d -5 through -2; Melphalan 140 mg/m2 d -2 |
| Consolidation | |
| Randomized arm A: DCEP | Dexamethasone 40 mg/d PO d 1-4; cyclophosphamide (300 mg/m2/d × 4 d) CI; etoposide (30 mg/m2/d × 4 d) CI; cis-platin (7.5 mg/m2/d × 4 d) CI every 3 months for 4 cycles |
| Randomized arm B | |
| DCEP* | Dexamethasone 40 mg/d PO d 1-4; cyclophosphamide (300 mg/m2/d × 4 d) CI; etoposide (30 mg/m2/d × 4 d) CI; cis-platin (75 mg/m2/d × 4 d) |
| CAD* | Cyclophosphamide (400 mg/m2/d × 4 d) CI; adriamycin (10 mg/m2/d × 4 d) CI; dexamethasone 40 mg/d PO d 1-4 |
| DPACE | Dexamethasone 40 mg/d PO d 1-4; cis-platin (75 mg/m2/d × 4 d) CI; adriamycin (10 mg/m2/d × 4 d) CI; cyclophosphamide (300 mg/m2/d × 4 d) CI; etoposide (30 mg/m2/d × 4 d) CI; every 3 months for 4 cycles. |
| DEX | In case of failure to recover platelets to at least 100 000/μL or failure to achieve >25% M-protein reduction with first cycle of DCEP in induction: DEX 40 mg d 1-4 every 28 d for 1 year. |
| Maintenance | |
| Interferon | 3 million U/m2 SQ 3 × wk plus first year of maintenance: Dexamethasone 40 mg every 3 months on d 1-4, 9-12, 17-20 |
| Second year onward; interferon alone |
CI indicates continuous infusion; SQ, subcutaneously.
†There was a protocol modification after entry of 121 patients (66 DCEP, 55 DCEP/CAD); see DPACE and DEX under total therapy 2.
In randomized arm B, DCEP was alternated with CAD every 6 weeks for 8 cycles.