Contiued from
PROSTATE CANCER: CHEMOTHERAPY
The PCRI has a protocol involving 5 days of continuous infusion Cytoxan at 600 mg/m2 a day coupled with 5-FU at 300 mg/m2 a day over 5 days. In addition, dexamethasone at 4 mg a day for 5 days is used as an antiemetic and an anticancer agent in this regimen. The medications are given continuously using a Port-A-Cath and a computerized Cadd Pump with cycles repeated every 21 days. Neupogen and Procrit are used to protect the bone marrow. There is rationale for this based on outstanding responses in "refractory" breast cancer patients as well as responses to cytoxan shown here. The dose of 600 mg/m2 a day for 5 days is equal to 3 grams per M2, the same dose employed by Smith et al. Of 21 patients, 6 had a 90% reduction in PSA. Survival information is needed.
Cytoxan: Bone Marrow Support
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21 patients: Cytoxan 3 grams/m2
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GM-CSF 5 ug/kg on days 3-10
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Lower dose if prior pelvic radiation
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6/21 (29%) with > 90% reduction in PSA
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No survival info in report
Smith DC et al. Hi-dose Cytoxan with GM-CSF in hormone-refractory prostatic carcinoma. 3rd Annual Pittsburgh Cancer Conference, November 19-20, 1992, p 12. |
Cytoxan: Exposure Time
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Servadio et al: 36 D-2 pts treated with orchiectomy, DES 3 mg/d + weekly Cytoxan and 5-FU at 10 mg/kg x 2 years, then 5 mg/kg x 2 years but given every 3 weeks for 2 years, then every 4 weeks thereafter.
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75% relief of bone pain
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Cumulative survival at 11 years 55.5%
Servadio C, Savion M, Mukamel E: Urology 30:352, 1987.
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The Servadio regimen combines weekly Cytoxan with weekly 5-FU in combination with DES and orchiectomy. It has been used for 11 years in Israel, with an outstanding cumulative survival rate of 55.5%.
It would seem prudent to advise patients to consider such regimens using combinations rather than to employ single-agent therapy. This might lead to significantly longer response times than the results we are currently getting. The above regimen, however, is difficult to truly evaluate without knowing the extent of bone disease in the treated group. If you recall the Labrie et al. data on ADT2 in the 1 to 5 bone lesion group, they had an 8-year median survival rate of 58%.Therefore, if the patients receiving the Servadio regimen were heavily weighted in the 1 to 5 bone lesion category, their responses would be in keeping with those of Labrie et al. and would raise the issue of whether the chemotherapy portion of the Servadio regimen added to the response. Cytoxan has also been used in combination with HDK by Pavlick et al. (see chemotherapy table). Their response to this combination is shown below.
Cytoxan: synergy with HDK
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27 patients treated with HDK + HC + Cytoxan 100 mg/m2 orally for 14 days.
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Median cycle every 28 days
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21/27 or 78% with 50% or > decline PSA
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Median PSA 68...median nadir PSA 5
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Median duration of response 9 months
Pavlick AC et al. Treatment of hormone refractory PC with HDK, HC & Cytoxan. Proc Am Clin Oncol: 15:A698, 1996 |
Oral Cytoxan given for 14 out of each 28 days is an effective regimen, especially if combined with other active agents like Adriamycin (as shown above). The median duration of response (MDR) in this study was 8 months. Cytoxan has also been administered with a histamine antagonist, DPPE. The latter agent is under study. The preliminary findings are shown below.
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Cytoxan: Exposure Time
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Cytoxan orally at 100 mg per M2 for 14 days of a 28 day cycle combined with Adriamycin intravenously at 30 mg per M2 on 1st and 8th day of each 28 day cycle
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32% partial response
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Median duration of response: 8 months (range 2-23)
Ihde DC et al. Effective treatment of hormonally unresponsive metastatic carcinoma of the prostate with Adria mycin and cyclophosphamide, Cancer 45:1310, 1980
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Cytoxan: Bone Marrow Support
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DPPE (histamine antagonist)- potentiates chemotherapy cytotoxicity yet protects bone marrow, intestinal tract & hair.
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20 patients with HRPC treated with Cytoxan at 600-800 mg/m2 I.V. once a week x 4.
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5/7 (71%) PR in soft tissue tumor.
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9/18 (50%) > 50% drop in PSA.
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11/13 (85%) PR or CR of bone pain.
Brandes LJ et al, DPPE in combination with cytoxan: an active, low toxixity regimen for metastatic hormonally unresponsive PC. JC Clin Onco 13:1398-403, 1995
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Emcyt Combinations: Emcyt + VP-16, Emcyt + Taxol, Emcyt + Taxotere
The use of Emcyt has been problematic for us due to the salt retention, increased risk of thrombosis necessitating routine anticoagulation, and the moderate frequent complaints of nausea and anorexia it causes. However, there are impressive response rates with various Emcyt combinations. A few are shown here.
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Emcyt + VP16
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PSA > 50% in 30/35 (85.7%)
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31 patients D-2
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Median age 70 (range 55-81)
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Emcyt 2 capsules twice a day, VP-16 at 50-mg twice a day; Rx x 14 days out of 28
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Median survival (acturial) 32 months
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Toxicity: hair loss in all, gastritis in others
Cruciani G: Proc Am Soc Clin Oncol 17:329a, 1998.
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Emcyt + Taxol
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17/32 (53%) with > or = 50% PSA decline
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Median survival 17.25 months
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Taxol 120/m2 (over 96 hrs) q 3 weeks
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Emcyt at 600 mg/m2 per day
Hudes GR et al: JCO 15:156-163, 1997.
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Continuation of PROSTATE CANCER: CHEMOTHERAPY