This post was triggered by Dale's post: "Leibowitz Protocol".
"Dr. Bob" may have moved on during the intervening 10 years, but I was intrigued by his use of Thalidomide & Lenalidomide to inhibit angiogenesis. Tumors cannot outgrow their blood supply unless they make extensions to existing blood vessel networks (angiogenesis).
(Coincidentally, my wife is about to begin using Revlimid for multiple myeloma.)
Lenalidomide is similar to Thalidomide, but with fewer side effects, such as peripheral neuropathy. Leibowitz used "thalidomide 50 mg one night, alternating with Revlimid 5 mg the next".
5mg is a low dose (available doses range from 2.5mg to 25mg).
First, the negative news. Lenalidomide & Docetaxel turns out to be a bad idea, as the Mainsail study discovered [1]:
"we randomly assigned chemotherapy-naive patients with progressive metastatic castration-resistant prostate cancer in a 1:1 ratio to receive docetaxel (75 mg/m(2)) on day 1 and prednisone (5 mg twice daily) on days 1-21 and either lenalidomide (25 mg) or placebo once daily on days 1-14 of each 21 day treatment cycle."
"At data cutoff (Jan 13, 2012) after a median follow-up of 8 months ... 221 patients had died: 129 in the lenalidomide group and 92 in the placebo group. Median overall survival was 17·7 months ... in the lenalidomide group and not reached in the placebo group".
But here is a thalidomide study (2009) [2], that used it as monotherapy in the off-phase of intermittent ADT [IADT]:
"Patients were randomized to 6 months of gonadotropin-releasing hormone agonist followed by 200 mg per day oral thalidomide or placebo (oral phase A). At the time of prostate specific antigen progression gonadotropin-releasing hormone agonist was restarted for 6 additional months. Patients were then crossed over to the opposite drug and were treated until prostate specific antigen progression (oral phase B)."
"During oral phase A the median time to PSA progression was 15 months for the thalidomide group compared to 9.6 months on placebo"
"The median time to PSA progression during oral phase B for the thalidomide group was 17.1 vs 6.6 months on placebo".
In a British study (2002) [3]:
"We undertook an open-label study using thalidomide 100 mg once daily for up to 6 months in 20 men with" CRPC.
"Three men (15%) showed a decline in serum PSA of at least 50%, sustained throughout treatment. Of 16 men treated for at least 2 months, six (37.5%) showed a fall in absolute PSA by a median of 48%."
From 2007 [4]:
"A total of 39 men with {metastatic CRPC} who had progression during or after at least 1 conventional cytotoxic drug were treated on a single-arm Phase II trial with dexamethasone, 0.75 mg twice a day plus thalidomide, 100-400 mg/day."
"Best-observed responses included >50% prostate-specific antigen (PSA) reduction with no radiologic progression: 10 of 39 (26%; 95% confidence interval 13% to 42%). An additional 14 of 39 had decreased PSA but then with radiologic or other progression by 12 weeks. Median progression-free survival was 84 days."
"PSA responses were frequent. Mostly, these were not durable, but some lasted more than a year.
In a phase I/II trial (2010) [5] at Johns Hopkins:
"Sixty men with non-castrate, nonmetastatic, biochemically relapsed prostate cancer were stratified by prostate-specific antigen (PSA) doubling time, surgery/radiation therapy, prior androgen deprivation therapy (ADT), and randomized to lenalidomide 5 mg (n = 26) or 25 mg/d (n = 34) for 3 weeks repeated monthly for 6 months or until dose-limiting toxicity or disease progression."
"The change in PSA slope was greater with 25 mg versus 5 mg ... With a mean follow-up of 31.4 months (range 14-44), five patients on 25 mg and one patient on 5 mg remain on the study."
An anecdotal German case (2012) [6]:
"Long-term disease stabilization in a patient with castration-resistant metastatic prostate cancer by the addition of lenalidomide to low-dose dexamethasone and celecoxib."
Another anecdotal case (2018) [7]:
"A 70‐year‐old Japanese man was referred to our hospital for the further examination of his urine retention. On his initial visit, his PSA level was 966 ng/mL, and a prostate needle biopsy was performed. Based on the diagnosis of Gleason score 4 + 4 = 8 prostate adenocarcinoma, bone scintigraphy, CT, and MRI, we diagnosed that his prostate cancer stage was T3bN0M1b. Combined androgen blockade therapy (CAB) using bicalutamide and leuprorelin acetate was started from May 2016 [Figs. [Figs.1,1, ,2,2, and and3].3]. At his initial examination, because a discrepancy between the total protein (12.3 mg/dL) and albumin (3.6 mg/dL) was observed, multiple myeloma was also suspected. His serum IgG level was elevated to 7126 mg/dL, and a bone marrow biopsy revealed multiple myeloma (IgG‐λ type). Despite an initial response, his PSA level rose again in August 2016. At the same time, because his multiple myeloma was also refractory to the initial chemotherapy of bortezomib, melphalan, and prednisolone (VMP), lenalidomide was introduced. His PSA level subsequently gradually decreased and remained low without any change in the CAB [Fig. [Fig.22]."
-Patrick
[1] ncbi.nlm.nih.gov/pubmed/257...
[2] ncbi.nlm.nih.gov/pubmed/191...
[3] ncbi.nlm.nih.gov/pubmed/126...
[4] ncbi.nlm.nih.gov/pubmed/176...
[5] ncbi.nlm.nih.gov/pubmed/209...
Pomi-T vs Pom Juice
