A 40 year old prisoner was referred to us after an Orchiectomy.
there is still a residual 10.6 cm retroperitoneal mass now know encasing the Aorta and major blood vessel
and invading the L4, L5. Threatening the spine stability in this area. The pain ihere is controlled with Medication. HCG 159. PET obtained show extension of the mass laterally, Nephrostomy bilaterally in place. Hct 27%, Hx of HTN
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some of the considerations and consulted Published notes follow:
will admit for the 1st Cycle of BEP
please contact us with questions;
1.how much we will reduce Cisplatin?
2.should attempt to resection be proposed?
3.or do you think RT after 4 cycles of BEP should do?
4.Is this patient at higher risk for secondary AML?
5.do we need a MRI of the brain?
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"Urology was consulted and recommended induction chemotherapy and consideration of surgical consolidation after chemotherapy. The case was discussed extensively at tumor board. The consensus was that cisplatin-based chemotherapy is an essential component of potentially curative treatment, so the planned treatment included reduced-dose etoposide and cisplatin with aggressive IV hydration along with renally dosed allopurinol given the bulk of the tumor."
Tim McCarthy.
A randomized trial of cisplatin, etoposide and bleomycin (PEB) versus carboplatin, etoposide and bleomycin (CEB) for patients with 'good-risk' metastatic non-seminomatous germ cell tumors.
Bokemeyer C1, Köhrmann O, Tischler J, Weissbach L, Räth U, Haupt A, Schöffski P, Harstrick A, Schmoll HJ.
Abstract
BACKGROUND:
Cisplatin-based combination chemotherapy will cure 70% to 80% of patients with metastatic non-seminomatous germ cell tumors but is associated with the possibility of severe neuro-, oto- and nephro-toxicities. Carboplatin, a cisplatin analogue, is an active drug in testicular cancer with a more favourable spectrum of side effects. In a randomized trial, the German Testicular Cancer Study Group compared a combination regimen of carboplatin, etoposide and bleomycin (CEB) to standard cisplatin, etoposide and bleomycin (PEB) chemotherapy for patients with 'minimal-' and moderate-disease' non-seminomatous germ cell tumors, according to the Indiana University classification.PATIENTS AND METHODS:
PEB was given for three cycles at standard doses (given days 1-5), and the CEB regimen consisted of carboplatin (target AUC of 5 mg/ml x min) on day 1, etoposide 120 mg/m2 on days 1 to 3 and bleomycin 30 mg on days 1, 8 and 15. Four cycles of CEB were given, with the omission of bleomycin in the fourth cycle. Thus, the cumulative doses of etoposide and bleomycin applied in the two treatment arms were comparable. Fifty-four patients were entered on the trial, 29 were treated with PEB and 25 with CEB chemotherapy. Patients were stratified according to disease extent (minimal versus moderate) and the degree of tumor marker elevation. Thirty-two patients (59%) belonged to the group with minimal disease and low markers.RESULTS:
No significant difference in response to chemotherapy was seen between the two arms, with CR rates of 81% for the PEB arm and 76% for CEB treatment. However, more patients treated with CEB (32% versus 13%) have relapsed after therapy, and 4 patients (16%) have died of disease progression after CEP in contrast to 1 (3%) after PEB therapy. The first interim analysis of negative events (relapse, vital tumor at secondary resection, death from disease and therapy-associated death) showed a significantly higher rate after CEB than after PEB therapy, and the trial was terminated early. After a median follow-up of 33 months for all patients, the calculation of negative events is still significantly in favour of PEB-treated patient, particularly since three late relapses > 2 years have been observed in the CEB arm (P = 0.03).CONCLUSION:
This randomized trial demonstrates that even with the use of adequate doses of etoposide and full-dose bleomycin, carboplatin cannot altogether replace cisplatin in patients with testicular cancer. Treatment with the PEB regimen remains the standard approach in patients with 'good-risk' non-seminomatous germ cell tumors.BEP
Regimen 1 (5-day schedule)
Bleomycin 30 U or 30 mg iv bolus d1, 8, 15 or d2, 9, 16
Etoposide (VP-16) 100 mg/m2/d iv over 1 h d1-5
Cisplatin (CDDP) 20 mg/m2/d iv over 1 h d1-5
Q3w x 3-4 cycles
Culine S et al. Randomized trial comparing bleomycin/etoposide/cisplatin with alternating cisplatin/cyclophosphamide/doxorubicin and vinblastine/bleomycin regimens of chemotherapy for patients with intermediate- and poor-risk metastatic nonseminomatous germ cell tumors: Genito-Urinary Group of the French Federation of Cancer Centers Trial T93MP. J Clin Oncol 2008; 26:421 (link to the article).
de Wit R et al. Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of 3- or 5-day schedule in good-prognosis germ cell tumor: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council. J Clin Oncol 2001; 19:1629 (link to the article).
Nichols CR et al. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B study. J Clin Oncol 1998; 16:1287 (link to the article).
Williams, SD et al. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med 1987; 316:1435 (link to the article).
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R.Miller et al! Cisplatin induced Nephrotoxicity!
==================================
1.Acute Renal failure
2.Hypomagnesemia
3.Hypocalcemia
4.Fanconi like Syndrome
5.Distal RTA
6.Renal salt wasting
7.Renal Concentration defect
8.Hyperuricemia
9.Erythropoietin deficiency
10Thrombotic Micro-angiopathy
11.Chronic Renal Failure
what is in store
----------------------
" Testicular Cancer
Initial chemotherapy
Salvage chemotherapy
Initial chemotherapy
Carboplatin (for stage I seminoma)
Carboplatin (Paraplatin) AUC 7 x 1 dose
Oliver RT et al. Radiotherapy versus carboplatin for stage I seminoma: updated analysis of the MRC/EORTC randomized trial (ISRCTN27163214). 2008 ASCO annual meeting. Abstract 1 (link to the abstract).
Oliver RT et al. Radiotherapy versus single-dose carboplatin in adjuvant treatment of stage I seminoma: a randomized trial. Lancet 2005; 366:293 (link to the article).
BEP
Regimen 1 (5-day schedule)
Bleomycin 30 U or 30 mg iv bolus d1, 8, 15 or d2, 9, 16
Etoposide (VP-16) 100 mg/m2/d iv over 1 h d1-5
Cisplatin (CDDP) 20 mg/m2/d iv over 1 h d1-5
Q3w x 3-4 cycles
Culine S et al. Randomized trial comparing bleomycin/etoposide/cisplatin with alternating cisplatin/cyclophosphamide/doxorubicin and vinblastine/bleomycin regimens of chemotherapy for patients with intermediate- and poor-risk metastatic nonseminomatous germ cell tumors: Genito-Urinary Group of the French Federation of Cancer Centers Trial T93MP. J Clin Oncol 2008; 26:421 (link to the article).
de Wit R et al. Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of 3- or 5-day schedule in good-prognosis germ cell tumor: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council. J Clin Oncol 2001; 19:1629 (link to the article).
Nichols CR et al. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B study. J Clin Oncol 1998; 16:1287 (link to the article).
Williams, SD et al. Treatment of disseminated germ-cell tumors with cisplatin, bleomycin, and either vinblastine or etoposide. N Engl J Med 1987; 316:1435 (link to the article).
Regimen 2 (3-day schedule)
Bleomycin 30 U or 30 mg iv bolus d1, 8, 15
Etoposide (VP-16) 165 mg/m2/d iv d1-3
Cisplatin (CDDP) 50 mg/m2/d iv d1-2
Q3w x 3-4 cycles
de Wit R et al. Equivalence of three or four cycles of bleomycin, etoposide, and cisplatin chemotherapy and of 3- or 5-day schedule in good-prognosis germ cell tumor: a randomized study of the European Organization for Research and Treatment of Cancer Genitourinary Tract Cancer Cooperative Group and the Medical Research Council. J Clin Oncol 2001; 19:1629 (link to the article).
EP
Etoposide (VP-16) 100 mg/m2/d iv over 1 h d1-5
Cisplatin (CDDP) 20 mg/m2/d iv over 1 h d1-5
Q3w x 4 cycles
Kondagunta, GV et al. Etoposide and Cisplatin chemotherapy for metastatic good-risk germ cell tumors. J Clin Oncol 2005; 23:9290 (link to the article).
VIP (for patients with underlying lung disease)
Etoposide (VP-16) 75 mg/m2/d iv over 1 h d1-5
Ifosfamide 1.2 g/m2/d iv d1-5
Cisplatin (CDDP) 20 mg/m2/d iv over 1 h d1-5
Mesna 120 mg/m2 iv bolus d1 before ifosfamide, followed by 1.2 g/m2/d civi d1-5
Filgrastim (Neupogen) 5 mcg/kg sc qd d7-16
Q3w x 4 cycles
Nichols, CR et al. Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B study. J Clin Oncol 1998; 16:1287 (link to the article).
Hinton, S et al. Cisplatin, etoposide and either bleomycin or ifosfamide in the treatment of disseminated germ cell tumors: final analysis of an intergroup trial. Cancer 2003; 97:1869 (link to the article).
Salvage chemotherapy (back to top)
VIP
Etoposide (VP-16) 75 mg/m2/d iv over 1 h d1-5
Ifosfamide 1.2 g/m2/d iv d1-5
Cisplatin (CDDP) 20 mg/m2/d iv over 1 h d1-5
Mesna 120 mg/m2 iv bolus d1 before ifosfamide, followed by 1.2 g/m2/d civi d1-5
Filgrastim (Neupogen) 5 mcg/kg sc qd d7-16
Q3w x 4 cycles
Loehrer, PJ Sr et al. Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide. Ann Intern Med 1988; 109:540 (link to the article).
McCaffrey, JA et al. Ifosfamide- and cisplatin-containing chemotherapy as first-line salvage therapy in germ cell tumors: response and survival. J Clin Oncol 1997; 15:2559 (link to the article).
VeIP (for patients who received prior etoposide)
Vinblastine 0.11 mg/kg/d iv over 1 h d1-2
Ifosfamide 1.2 g/m2/d iv d1-5
Cisplatin (CDDP) 20 mg/m2/d iv over 1 h d1-5
Mesna 400 mg/m2 iv 15 min before first ifosfamide dose, followed by 1.2 g/m2/d civi d1-5
Q3w x 4 cycles
Loehrer, PJ Sr et al. Salvage therapy in recurrent germ cell cancer: ifosfamide and cisplatin plus either vinblastine or etoposide. Ann Intern Med 1988; 109:540 (link to the article).
Loehrer PJ, Sr et al. Vinblastine plus ifosfamide plus cisplatin as initial salvage therapy in recurrent germ cell tumor. J Clin Oncol 1998; 16:2500 (link to the article).
TIP
Paclitaxel (Taxol) 250 mg/m2 iv over 24 hrs d1
Ifosfamide 1.5 g/m2/d iv over 1 h d2-5
Cisplatin (CDDP) 25 mg/m2/d iv over 30 min d2-5
Mesna 500 mg/m2 iv before ifosfamide, and at 4 and 8 hrs after ifosfamide daily, d2-5
Filgrastim (Neupogen) 5 mcg/kg sc qd d7-18
Q3w x 4 cycles
Kondagunta, GV et al. Combination of paclitaxel, ifosfamide, and cisplatin is an effective second-line therapy for patients with relapsed testicular germ cell tumors. J Clin Oncol 2005; 23:6549 (link to the article).
Cisplatin + Epirubicin
Cisplatin (CDDP) 20 mg/m2/d iv d1-5
Epirubicin 90 mg/m2 iv over 15-30 min d1
Filgrastim (Neupogen) 5 mcg/kg sc qd d7-16, or pegfilgrastim 6 mg sc d7
Q3w x 4 cycles
Bedano P et al. Phase II study of cisplatin plus epirubicin salvage chemotherapy in refractory germ cell tumors. J Clin Oncol 2006; 24:5403 (link to the article).
Paclitaxel + Gemcitabine (for platinum-refractory disease)
Paclitaxel (Taxol) 100-110 mg/m2 iv over 1 h d1, 8, 15
Gemcitabine (Gemzar) 1000 mg/m2 iv over 30 min d1, 8, 15
Q4w x 6 cycles
Einhorn LH et al. Phase II study of paclitaxel plus gemcitabine salvage chemotherapy for germ cell tumors after progression following high-dose chemotherapy with tandem transplant. J Clin Oncol 2007; 25:513 (link to the article).
Hinton, S et al. Phase II study of paclitaxel plus gemcitabine in refractory germ cell tumors (E9897): a trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2002; 20:1859 (link to the article)."
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