The Logothetis Protocol

In response to a question on the PPML regarding the “Logothetis Protocol”, Dr. Strum wrote:

I will respond with a generic response by posting a review of the Logothetis protocol we have written up for patients. Multiple agent chemo requires SKILL on the part of the oncologist. Without it the patient has INCREASED risk of infection and other side effects from the chemo agents used. Even with excellent training the risk of infection secondary to marrow suppression exists. This follows:

Dr. Christopher Logothetis has combined the two most active chemotherapy regimens into one protocol alternating regimens. Preliminary indications are that the combination may be substantially more active than the two parts given individually. Three cycles are recommended in the adjuvant setting. Patients with advanced disease are given one cycle and monitored for effect on the PSA.

Patients with advanced disease that respond are continued on therapy as long as there is a continuing benefit without excessive toxicity.

Chemotherapy: Cycle length = 56 days (8 weeks)

• Adriamycin 20 mg/m2 IV day 1, 15, 29
• Ketoconazole 400 mg orally three times a day for days 1-7, 15-21, 29-35
• Vinblastine 4 mg/m2 IV day 8, 22, 36
• Estramustine 140 mg orally three times a day for days 8-14, 22-28, 36-42
• Rest period from day 43 to 56 then restart next cycle

Supportive medications:

• Hydrocortisone 20 mg orally in am and 10 mg in pm (take with food)
• Coumadin dosed to maintain an INR between 1.75 and 2.25
• Neupogen 300 mcg s.q. twice a week except during the rest period
• Epogen 10,000 units s.q. three times a week as needed to avert anemia
• Kytril 0.7mg with each dose of Velban or Adriamycin
• Decadron 10 mg with each dose of Adriamycin

Laboratory Tests:

• CBC blood test on the day of each injection and day #10 of the first cycle
• Chemistry panel once a month and day #14 of the first cycle
• PSA and PAP once a month
• Prothrombin time weekly

Precautions:

• Ketoconazole CANNOT be taken with Seldane, Claritin, Hismanil, or any long-acting antihistamines because it may cause serious heart problems.
• Propulcid also must be avoided.
• Ketoconazole and Estramustine should be taken on an empty stomach (30 min. before or 2 hours after food ) or they will not absorb from the stomach.
• Ketoconazole can not be take with the following drugs: Prilosec, Zantac, Tagamet or any other antacids since the Ketoconazole will not be absorbed.

Side Effects:

• Non-specific lassitude and tiredness may occur.
• Hair loss to some degree is common.
• Temporary mouth sores and/or diarrhea is unusual but can occur.
• Adriamycin and Velban can cause low blood counts which can increase the risk for serious infection. It is critical that weekly CBC tests are obtained to guide chemotherapy and Neupogen dosing. Any fever greater than 100.5 should be called to your M.D. immediately day or night.
• Velban can cause numbness and tingling in the hands and feet.
• Velban has caused temporary malfunction of the intestines resulting in bloating (ileus). We recommend a small dose of milk of magnesia on the day of Velban therapy.
• Ketoconazole and Estramustine can cause nausea and upset stomach but with use of anti-nausea drugs this should NOT occur.
• Estrogen in Estramustine can cause blood clots thus the need for Coumadin.
• Adriamycin, if it is used for more than one year, can occasionally cause weakening of the heart muscle.
• Adriamycin and Velban, if they are improperly injected into the skin (outside of the vein), can cause severe skin reactions and ulcers.
• Ketoconazole can cause hepatitis thus the need to do monthly Chemistry
• Hydrocortisone can cause adrenal atrophy so when the protocol is stopped the hydrocortisone must be tapered off