Taxol or Taxotere?

I have successfully experienced three cycles of weekly Taxotere (48 TXs) during two years; followed by sequencing Novantrone (6 TXs of Q21), one month of daily Cytoxan po, seven TXs of weekly Emcyt + Velban, four weeks of weekly Adriamycin, and currently five TXs of weekly (3/4) Emcyt @ 140 mg tid, D0, D1, D+1 + Taxol @ 50 mg/m2---PSA beginning Emcyt + Taxol = 145; present (3/19/03) PSA = 115-----not a roaring success, but a  decided improvement from a monthly PSADT (PSA doubling time).

I have now experienced both Taxotere and Taxol and although Taxol is the older taxane and is successfully used in protocols for most cancer types, I have found Taxol to be one of the most difficult chemo agents to tolerate of the seven agents I have tried as I sequence through the PCa protocols.

I believe that the issue is not the chemo element of Taxol, but the preservatives/carriers in the formula which require significant pre-meds  required to prevent ‘...allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthematic episodes in certain susceptible people.’ (1)  Pre-meds for Taxol are: 20 mg Decadron po 12 hours, and again 6 hours before TX, + 20 mg Decadron IV, + 300 mg Tagamet IV*, + 50 mg Benadryl**----all before TX and requiring about one hour, followed by the Taxol TX; total elapsed time = 3-4 hours.  Pre-med for Taxotere is only:  6-10 mg Decadron IV (vs. 60 mg for Taxol), wait 15 minutes, check blood pressure, and TX over one hour.  I completed 48 TXs of Taxotere with no incidents; in my first Taxol TX I experienced severe allergic reactions requiring significant additional time and meds to counter the reactions.  Each successive TX has been difficult, requiring greatly extended infusion time (much slower rate) and frequent stoppages due to early-stage allergic reactions.

In trying to determine my possible chemo sequencing strategy, as a section of my January 2001 position paper A Patients Perspective on Chemotherapy - Part 2,  I researched and analyzed ‘Taxol vs. Taxotere’ as follows (to search the referenced citations, see the above paper):

..... “What is next?  My medical oncologists suggests weekly Taxol because he believes it might be less toxic.  But----

We all see statements on the Internet that Taxotere is 100 times stronger than Taxol.  I assume this originated from some studies that reported that Taxotere, in vitro, was 100-fold more potent than Taxol in bcl-2 phosphorylation (17) and apoptotic cell death. (11)  Bcl-2 is considered the ‘guardian of microtubule integrity’ and Taxotere is capable of inducing bcl-2 phosphorylation and cell death at 100-fold lower concentrations than Taxol. (18)  But Stein (19) says that Taxotere has a somewhat higher affinity for microtubules than Taxol (approximately two-fold) and in some circumstances may be a more potent inducer of bcl-2 phosphrylation, however, it is not clear whether these Taxotere-events are directly related to its anti-prostate cancer effects.  Garcia (20) reported that the effects of Taxotere as compared to Taxol appeared at a two-fold lower concentration.  A pharmacology sheet says that Taxotere, like Taxol, prevents the mitotic spindle from being broken down by stabilizing the microtubule bundles, but clinical trials indicate it is about twice as effective as Taxol in doing so. (21)

So, is Taxotere 100-fold more potent than Taxol, or two-fold more potent, or is the transformation of bcl-2 related to anti-prostate effects?  In general, the taxane protocols call for Taxol at twice the mg/m2 of Taxotere.  Both drugs stabilize cellular microtubules and thus, interfere with mitosis (reproduction) and cause cell death.  Taxotere has linear pharmacokinetics, a longer plasma life, and longer intercellular retention. (22)   Based on the above analysis Taxotere is my drug of choice, if I have a choice.

Regarding toxicities, Hortobagyi (11) states that potential advantages of Taxotere over Taxol include reduction in peripheral neuropathies and lack of arthalgia (joint pain)/myalgia (muscular pain) syndrome.  Unless my medical oncologist has different citations, I doubt that Taxol is less toxic than Taxotere and if I have one, Taxotere is still my drug of choice notwithstanding the toxicities.

One interesting recent trial combined weekly Taxotere @ 35 mg/m2 + weekly Taxol @ 65 mg/m2 for 4 weeks, dubbed a ‘taxane package’. (23)  In this study Lokich reports that this dosing protocol increases the taxane dose intensity by a factor of 1.65 over normal dosing and thus, increases the taxane cytotoxic injury and takes advantage of the fact that the two agents lack complete cross-resistance; if some tumors are nonresponders to one of the agents, the other will zap it, and vice versa.  Interesting salvage therapy if you fail either of the drugs?”.......

Now that I have experienced both taxoid drugs, I have studied the spec sheets included with the infusion packages of both and believe that the added toxicities and required cocktail of pre-meds for Taxol protocols are due to the formulation of the drug.

Both of the taxanes were break-through drugs for cancer with the highest response rates (RR) and median duration of responses (MDR), and they extended median duration of survival (MDS) when compared to the older chemo agents.  Both taxanes are anticancer active by virtue of binding to tubulin and thus, interfering with microtubule assembly which is necessary for growth----they ‘freeze’ the microtubule assembly and thus interfere with mitosis (growth).

TAXOL (1) ---- is a natural product with antitumor activity and extracted from the Taxus species (evergreen needles)--it is highly lipophilic (capable of dissolving), but insoluble in water---each 1 mL vial is composed of 6 mg of Taxol, 527 mg of ployxyethylated castor oil, 49.75% (v/v) dehydrated alcohol, USP, sodium metabisulfite and sterile water for injection.  The major ingredient causing the allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic (difficult breathing) episodes seems to be the sodium metabisulfite (see ref 2).

After about 10 minutes into my first Taxol infusion I suddenly pitched forward, had difficulty breathing, became temporarily partially blind and deaf,  nauseated, extremely flushed in my face/head and chest, lost most cognitive abilities, and had a searing stabbing back/spine pain from my belt-line to my coccyx---since the onc nurse stays with you for the first 15 minutes of TX,  she immediately stopped the infusion and called the emergency call---within 30 seconds the room was filled with most of the staff and multiple additional meds were infused into my port---after approximately 30 minutes, I returned to ‘normal’ and slowly completed the TX in about 3 hours----for my subsequent TXs, notwithstanding all the pre-meds, the infusion is very slow and consumes about 2 hours, with stoppages when I feel the onset of any allergic reactions.

Taxotere  (2)---is prepared by semisynthesis with a precusor extracted from the renewable needle biomass of yew plants---(sometimes referred to as a synthetic taxane)---each 1 mL is composed of 40 mg of docetaxel (anhydrous) and 1040 mg of polysorbate 80----polysorbate 80 is a common emulsifier, an agent used to make an emulsion of a fixed oil.  The only pre-meds recommended are corticosteroids (Decadron) and the hypersensitivity reactions seem to be 2.2% of patients experience hypotension, broncospasm, and possibly a rash; nothing as severe as the possibilities of the allergic reactions to Taxol.

During 48 TXs of Taxotere and pre-med of only 6-10 mg of Decadron IV, I had no such events; I have had adverse reactions during all Taxol TXs, notwithstanding the significant pre-meds.

In summary---a Taxol infusion consists of... a 1 mL vial is composed of : 1)  6 mg of Taxol, 2)  527 mg of ployxyethylated castor oil, 3)  49.75% (v/v) dehydrated alcohol, USP, sodium metabisulfite, and sterile water for injection.  ----a Taxotere infusion consists of... a 1 mL is composed of: 1)  40 mg of docetaxel (anhydrous) and, 2) 1040 mg of polysorbate 80, a common agent used to make an emulsion of a fixed oil.

My question to myself is whether my reaction to Taxol is unique, or am I chemo-saturated and possibly reaching the end of tolerance for treating my disease with cytotoxic chemo agents?  My conclusion is that Taxotere is not only at least 2-fold more effective and patient-friendly than Taxol, but is also much more tolerable and significantly less toxic.

Bill Aishman      March 2003

Note:  I am not a doctor and I can not render medical advice.  I am a prostate cancer patient in late-stage disease and performed this analysis for my own decision-making process.  I make no claim that this review is definitive, complete or authoritative and I request any contributions to, or clarification of the subject which might contribute to the issue or inquiry.  In conjunction with a medical team, every cancer patient must make their own decisions regarding treatment options.

* Tagamet; histamine H2 blocker---prevents disorders of the stomach (nausea).

(1)   Patient Information Leaflet; enclosed with Taxol infusion package; revised June 2001.

(2)   Patient Information Leaflet; Questions and Answers About Taxotere for Injection Concentrate; enclosed with Taxotere infusion package; Rev 11/01.