Strum on cytozan and servadio protocol from htlm of old hrpca site an old old paper but still servadio shows 50+% survival in D2 Pca @15yrs

Cytoxan is often-studied as an agent for the treatment of PCa (PCRI - Sept 1997; See the writeup at the following url:

prostate-cancer.org/educati...

Dr. Strum reports a trial of HDK with oral Cytoxan had a RR of 78% and an MDR of 9 months (Proc Am Soc Clin Oncol:15:A698, 1996); and another study of Cytoxan at 600-800 mg/m2/wk for four weeks + DPPE (a histamine antagonist) wherein 20 patients had a 50% RR (J Clin Oncol 13:1398-403, 1995). In 1997 Dr. Strum concluded that “Cytoxan is an extremely active chemotherapeutic agent for the treatment of prostate cancer.” The Lupus Foundation of America, Inc. states that Cytoxan is a dangerous drug because patients ‘...have an increased risk of developing malignancies including leukemia, bladder cancer, and other tumors.’ as a long term result of the use of the drug. However, there are some medical oncologists that are combining Cytoxan with Adriamycin as salvage therapies following failure of other more common treatments.

Cytoxan is a ‘high-response’ agent in prostate cancer. When combined with Adriamycin @ 40 mg/m2 + G-CSF Small et al. (JCO 14;1617-25, 1996) reported a RR of 46% and MDS of 23 months. Pavilck et al. (Proc. Am. Clin. Oncol.;15A698, 1996) combined Cytoxan @ 100 mg/m2 orally/14 days; cycle 28 days with HDK for a 78% RR and 9 month MDR.

The Servadio protocol has been used since 1980 in Israel with a cumulative survival rate of 55.5%. This protocol is often mentioned but seldom utilized. Why? Servadio, Nissenkorn, Mukamel first reported the concept in 1980 (Urology 1980 Sep;16(3):257-60) combining orchiectomy + DES (3 mg/day) + Cytoxan + 5-FU (10 mg/kg X 2 years; then 5 mg/kg X 2 years); 50% tumor shrinkage in 84% of patients; cumulative survival rate during 3.5 years was 76.5%. Servadio et al. again reported in Urology 1983 May;21(5):493-5 of 24 Stage D patients and the same hormonal/chemotherapy protocol a 79.1% tumor shrinkage, stabilization/partial disappearance of osteoblastic lesions; cumulative survival rates at 5 and 6 years were 63.48 and 50.78 %, respectively. Servadio again reported in Urology 1987 Oct;30(4):352-5 of 36 D2 patients on the same protocol; 75% had bone pain relief; 80% had urinary symptom relief; 82.2% regression or stabilization of the primary tumor; 55.5% stabilization/disappearance of osteoclastic lesions; cumulative survival rate at 11 years is 55.5%. Again in 1992, Servadio et al. reported in Urology 1992 Mar;39(3):274-6 a retrospective 15 year review of his protocol of hormonotherapy: 50 D2 patients treated on diagnosis; 28% died of the disease; 28% died of other causes; 40% are still alive (14% with clinical disease); he suggests continuation of the protocol utilizing the newer chemotherapeutic agents.

The Servadio protocol is well documented and represents the longest survival statistics. Servadio continually reports that this early aggressive combined systemic therapy intervention in D2 patients is well tolerated with only minimal temporary side effects. One wonders why it has not been investigated and utilized in the U.S. Servadio began his protocol on diagnosis of D2 with an orchiectomy, but with the advent of Lupron/Zoladex, this would no longer be a necessity and the chemotherapy agents combined in the protocol are well-known and in multiple use in other pharmacokinetic combinations. Dr. Strum suggests that the Servadio protocol is ‘over-treatment’ since perhaps surgical or medical castration alone might provide similar survival, but this patient suggests that the Servadio protocol results are well documented, while other theories are not.

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  • But...do the risks out way the benefits. I've been reading a lot of material on how chemo (any chemo) kills the daughter cells, but not the stem cells. This process allows the stem cells to breed stronger and more resistant cancer post treatment. Chemo may work for the types of cancer that respond to the point of eradication (some leukemias...Hogkin's lymphoma...etc) but not for cancers like prostate...ovarian...etc. So are we signing our death warrants by inadvertently strengthening our cancer by teaching it to resist? Our regular cells will resist if exposed to a toxin long enough...we develop an immunity ...so...wouldn't our cancers develop the same immunity. I've done chemo twice now. My PSA is low ...now...but as it always does...it'll be back and I fear...with a vengeance. I'm am scheduled for Xofigo along with a possible trial for Keytruda. I am thinking of not going thru with it. I know what the alternative is...but I am really having a hard time reconciling all of this. Am I just allowing big pharma the opportunity to make money of my insurance while I the disease does what it's going to do anyway...progress?

  • It is hard to tell, all we can do is keep on keepin on, get up every day and put one foot in front of the other, and hopefully we will have a cure for this disease one day soon. Where is your Keytruda trial? PD1 inhibitors are all the rage now.

    Dan

  • Dana Farber in Boston