AI's and Nolvadex together?

[A50#]

Anyone have any literature on why not to run Nolva with AI's like Letrozole and Arimidex? I've heard people say that it makes one or the other ineffective. I recently had a friend diagnosed with breast cancer, when I went to her visit I ran that by her doctor and he said he didnt think there was an interference between the two. He said they recommend one or the other so they know what treatment is working. He explained if you were taking both, you wouldnt know what treatment was effective. Anyones thoughts on this?

 

[Bigfella]

This is an interesting one

Impact of Tamoxifen on the Pharmacokinetics and Endocrine Effects of the Aromatase Inhibitor Letrozole in Postmenopausal Women with Breast Cancer

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An old study suggesting no benefit to this combo

Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial.
Baum M, Budzar AU, Cuzick J, Forbes J, Houghton JH, Klijn JG, Sahmoud T; ATAC Trialists' Group.
Erratum in

* Lancet 2002 Nov 9;360(9344):1520.

Abstract
BACKGROUND:

In the adjuvant setting, tamoxifen is the established treatment for postmenopausal women with hormone-sensitive breast cancer. However, it is associated with several side-effects including endometrial cancer and thromboembolic disorders. We aimed to compare the safety and efficacy outcomes of tamoxifen with those of anastrozole alone and the combination of anastrozole plus tamoxifen for 5 years.
METHODS:

Participants were postmenopausal patients with invasive operable breast cancer who had completed primary therapy and were eligible to receive adjuvant hormonal therapy. The primary endpoints were disease-free survival and occurrence of adverse events. Analysis for efficacy was by intention to treat.
FINDINGS:

9366 patients were recruited, of whom 3125 were randomly assigned anastrozole, 3116 tamoxifen, and 3125 combination. Median follow-up was 33.3 months. 7839 (84%) patients were known to be hormone-receptor-positive. Disease-free survival at 3 years was 89.4% on anastrozole and 87.4% on tamoxifen (hazard ratio 0.83 [95% CI 0.71-0.96], p=0.013). Results with the combination were not significantly different from those with tamoxifen alone (87.2%, 1.02 [0.89-1.18], p=0.8). The improvement in disease-free survival with anastrozole was seen in the subgroup of hormone-receptor-positive patients, but not the receptor-negative patients. Incidence of contralateral breast cancer was significantly lower with anastrozole than with tamoxifen (odds ratio 0.42 [0.22-0.79], p=0.007). Anastrozole was significantly better tolerated than tamoxifen with respect to endometrial cancer (p=0.02), vaginal bleeding and discharge (p<0.0001 for both), cerebrovascular events (p=0.0006), venous thromboembolic events (p=0.0006), and hot flushes (p<0.0001). Tamoxifen was significantly better tolerated than anastrozole with respect to musculoskeletal disorders and fractures (p<0.0001 for both).
INTERPRETATION:

Anastrozole is an effective and well tolerated endocrine option for the treatment of postmenopausal patients with hormone-sensitive early breast cancer. Longer follow-up is required before a final benefit:risk assessment can be made.
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The effect of tamoxifen on the pharmacokinetics of letrozole in female rats.
Tao X, Brodie AM, Nnane IP.
Source

Temple University School of Pharmacy, Philadelphia, PA, USA.
Abstract

The effects of single doses of tamoxifen (TAM; 0.5-5 mg/kg, i.v.) and chronic pretreatment with TAM (0.1-5.0 mg/kg/day, i.p. for 7 consecutive days) on letrozole (0.5 mg/kg, i.v.) pharmacokinetics were evaluated in female Sprague-Dawley rats. The plasma concentration-time profiles of letrozole (0.1-2.0 mg/kg) after single i.v. doses were analysed by the non-compartment model with terminal half-lives (t(1/2,lambdaz)) ranging from 34.3 to 37.5 h. The volume of distribution at the terminal phases (Vd(lambdaz)) ranged from 1.9 to 2.1 l/kg and clearance (CL) varied from 0.036 to 0.042 l/(h.kg). After co-administration of TAM and letrozole intravenously, the t1/2, Vd(lambdaz) and CL of letrozole were not significantly altered. Chronic pretreatment with TAM significantly decreased the t1/2 of letrozole by about 33%, and increased its clearance by an average of 40%. However, TAM pretreatment did not significantly affect the Vd(lambdaz) of letrozole in female rats. Co-administration of letrozole and TAM orally increased the absorption half-life of letrozole threefold although the absolute bioavailability remained unchanged. These observations suggest that single oral doses of TAM delay the absorption of letrozole while chronic pretreatment with TAM accelerates the elimination of letrozole, probably due to induction of cytochrome P450 enzymes in rats.

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Bigfella.

 

[Bigfella]

I think the general concencus especially within the particular field of your interest would suggest that the addition of Tamoxifen to an AI treatment schedule is likely to have no effect or be negative so isn't really worth the risk and best to stick with a single treatment which is most case appropriate.

Best wishes to your friend bro, I hope everything works out well......

Bigfella.

 

[Bigfella]

BTW I think you will find many bodybuilders misconstrue the data from studies like those above to suggest that because Tamoxifen reduces the effect of the AI, that is reason to not combine them in treatment for gyno etc and this is often posted on the boards as reason not to combine them.

The difference in our case for me is that although a combination may reduce the AI's effect, when treating gyno, we are better to try and attack it directly at receptor level with the SERM and indirectly with the AI to prevent further problems through inhibition of aromatase, even though the effects are reduced this can be compensated for with increased AI dose and is more a necessity.

Hope that helps mate

Bigfella.

 

[Kaladryn]

1. AI's and Novadex are very often used in combination to treat breast cancer, AI's are generally introduced after a year to two after starting nolvadex (depending on response), and then the two are taken concurrently.

2. There are a crapload of studies on taking the two together, however they are all on postmenopausal women. AI's eradicate nearly all estradiol in this group, men are completely different. AI's do show improved survivability when taken together with nolvadex in most studies on breast cancer.

3. It is true that the two taken together slightly reduce the effectiveness of each, however the combination is FAR more powerful than just one or the other. The reason why is that you can only reduce E2 by a little more than half with an AI in males, and increasing doses gives diminishing reductions. The combo allows a much higher reduction in the effects of E2.