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发表于 2013-5-6 20:44:23
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来自： 中国天津
小沈 发表于 2013-5-6 19:43 
呵呵，我通过链接查找HYPERCVAD的周期，查了两天，都没能找到，隔行如隔山，感觉在大海中捞针般。
不知道 ...
其实，你也行，只是动力还不够。总共就没有多少篇参考文献，不是大海捞针，而是金鱼缸里捞鱼。
NCCN中涉及HYPERCVAD的最初文献是这个，出自很权威的地方：
J Clin Oncol. 1999 Aug;17(8):2461-70.
Hyper-CVAD program in Burkitt's-type adult acute lymphoblastic leukemia.
Thomas DA, Cortes J, O'Brien S, Pierce S, Faderl S, Albitar M, Hagemeister FB, Cabanillas FF, Murphy S, Keating MJ, Kantarjian H.
SourceDepartments of Leukemia, Hematopathology, and Lymphoma, The University of Texas M.D. Anderson Cancer Center, Houston, TX, USA.
Abstract
PURPOSE: To evaluate response and outcome with a front-line intensive multiagent chemotherapy regimen in adults with Burkitt's-type acute lymphoblastic leukemia (B-ALL).
PATIENTS AND METHODS: From September 1992 to June 1997, 26 consecutive adults with newly diagnosed untreated B-ALL received hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD). Their median age was 58 years (range, 17 to 79 years), and 46% were > or = 60 years. Patients received Hyper-CVAD alternated with courses of high-dose methotrexate and cytarabine. Granulocyte colony-stimulating factor and prophylactic antibiotics were administered for all eight planned courses. CNS prophylaxis alternated intrathecal methotrexate and cytarabine on days 2 and 7 of each course.
RESULTS: Complete remission (CR) was obtained in 21 patients (81%). There were five induction deaths (19%). The median time to CR was 22 days (range, 15 to 89 days); 70% achieved CR within 4 weeks. The 3-year survival rate was 49% (+/- 11%); the 3-year continuous CR rate was 61% (+/- 11%). Twelve CR patients (57%) were in continuous CR at a median follow-up of 3+ years (range, 13+ months to 6.5+ years). Characteristics predicting for worse survival were age > or = 60 years, poor performance status, anemia, thrombocytopenia, peripheral blasts, and increased lactate dehydrogenase level. The 3-year survival rate was 77% for 14 patients younger than 60 years and 17% for 12 patients > or = 60 years (P <.01). Regression analysis identified older age, anemia, and presence of peripheral blasts as independent factors associated with shorter survival. Patients could be stratified according to (1) no or one adverse feature, (2) two adverse features, and (3) all adverse features. The 3-year survival rates were 89%, 47%, and 0%, respectively (P <.01).
CONCLUSION: Hyper-CVAD is effective in adult B-ALL. Identification of patients with high risk for relapse and improved methods to detect residual disease may result in risk-oriented approaches.
用GOOGLE可以找到全文，见附件。
其中你最关注的给药方案与剂量调整依据如下（好复杂，看着就头大，你凑合着点吧）：
Therapy
Therapy consisted of eight courses of alternating intensive chemotherapy. Odd courses (1, 3, 5, and 7) consisted of Hyper-CVAD: (1) hyperfractionated cyclophosphamide 300 mg/m2 intravenously (IV) over 2 hours every 12 hours for six doses on days 1 to 3, with mesna 600 mg/m2/d IV via continuous infusion on days 1 to 3 beginning 1 hour before cyclophosphamide and completed by 12 hours after the last dose of cyclophosphamide; (2) vincristine 2 mg IV on days 4 and 11; (3) doxorubicin 50 mg/m2 IV over 2 hours via central venous catheter on day 4; and (4) dexamethasone 40 mg daily either orally or IV on days 1 to 4 and days 11 to 14. The first course was accompanied by appropriate IV hydration and alkalinization (eg, dextrose in one-half normal saline plus sodium bicarbonate 100 mEq/L, to run at 100 to 150 mL/h, ie, 2.5 to 3 L/d; furosemide 20 to 40 mg was administered every 12 to 24 hours to keep adequate intake–output) and allopurinol to reduce the incidence of tumor lysis syndrome. Even courses (2, 4, 6, and 8) consisted of MTX and ara-C: MTX 1 g/m2 IV over 24 hours on day 1, and ara-C 3 g/m2 over 2 hours every 12 hours for four doses on days 2 and 3. Intravenous alkalinization was used to promote excretion of MTX in all courses. Calcium leucovorin was administered at a dose of 50 mg IV starting 12 hours after the completion of MTX and continued at a dose of 15 mg IV every 6 hours for eight doses until MTX blood levels were less than 0.1μmol/L. An algorithm of additional leucovorin rescue (50 mg IV every 6 hours) was followed if MTX blood levels were elevated (monitored at end of infusion [0 hour] > 20μmol/L, 24 hours > 1μmol/L, 48 hours > 0.1μmol/L). The IV formulation was supplemented with oral sodium bicarbonate on days 1 to 3. Oral acetazolamide was used to promote excretion if the urine pH was less than 7.0.
Standard dose reductions were as follows: (1) ara-C to 1 g/m2 for age ≥ 60 years, creatinine level greater than 2 g/dL, or MTX level at 0 hour more than 20μmol/L; (2) vincristine to 1 mg for total bilirubin level greater than 2 g/dL; (3) doxorubicin by 25% for bilirubin level 2 to 3 g/dL, by 50% for bilirubin level 3 to 4 g/dL, and by 75% for bilirubin level greater than 4 g/dL; (4) MTX by 50% for creatinine level greater than 2 g/dL, by 75% for creatinine level greater than 3 g/dL, or by 50% to 75% for delayed excretion and/or nephrotoxicity with a previous course (the degree of reduction dependent on the severity); and (5) elimination of doxorubicin in the first course in patients with small bowel or gastric involvement to reduce the length of myelosuppression and risk of perforation (n = 3).
Granulocyte colony-stimulating factor was initiated at least 24 hours after chemotherapy was completed at a dose of 10μg/kg subcutaneously daily and continued until the total WBC count was ≥ 3 × 109/L. Dose-intensity was maintained with subsequent courses initiated when the total WBC count was ≥ 3 × 109/L and the platelet count was ≥ 60 × 109/L after a waiting period of 24 hours after discontinuation of granulocyte colony-stimulating factor. If the WBC count was ≥ 3 × 109/L but the platelet count was less than 60 × 109/L on day 21, granulocyte colony-stimulating factor administration was held if the WBC count reached 30 × 109/L and hematologic profiles were obtained every 3 days until platelet recovery. Completion of eight courses on a schedule of every 21 days or earlier if count recovery occurred (but at least 14 days from the last course) would be expected to take 5 to 6 months. No maintenance therapy was administered.
CNS prophylaxis included alternating intrathecal administrations of MTX 12 mg (6 mg only via Ommaya) on day 2 and ara-C 100 mg on day 7 of each course for all eight courses (16 intrathecal injections).27 Therapy for CNS leukemia resulted in augmentation of intrathecal therapy during the induction course to twice weekly until the CSF cell count was normalized and the cytologic examination was negative for evidence of malignant cells; the program was then resumed as for prophylactic therapy. No prophylactic cranial irradiation (XRT) was administered, although therapeutic XRT could be administered if indicated. Four patients received therapeutic XRT to the base of the skull with 30 Gy administered over 2 weeks in addition to intrathecal therapy for documented CNS involvement and cranial nerve palsy. Other extramedullary sites of disease were treated as appropriate; one patient received consolidation XRT to a lytic lesion of the femur.
其他还有数篇相关文献，你可以用同样的方法查询。 |
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