Medical Chronotherapy for cancer?

[heblaj01]

In this article Which can be viewed as text or video (by the patient telling her story), a description is provided of a single case of advanced pancreas/liver cancer treatment timed on the patient biorythms (rather than according to hospital schedules) to get maximum effectiveness:
http://www.wbir.com/news/health/stor...?storyid=35474

I have read other articles mentioning the fact that nightime is the period of time when the immune system is the least effective & when cancer is proliferating the most. So that pills with a short half life are thought to be more effective when taken at bed time: this the recommandation made for instance by one University of Washington MD for the off label use of Artemisinin (a drug normally used to treat malaria) to fight cancer.
In the case of drugs with a long half life like Herceptin I don't see an advantage for chronotherapy, not to mention the problems of I.V. scheduling in hospitals which in general are not organized for chronotherapy.

[R.B.]

From the very little I have read on this subject the body does have biorythms, and it would be a reasonable assuption that drugs might be more "effective" deilvered at one point or another.

Re night time. Do yo have any links for these articles.

From the little I have read the bodies systems are dampened down at night / sleep. Melatonin is reported as a powerful antioxidant of long chain fats. Does this dampen down activity in the brain and what activity - prepuberty children are reported as having higher melatonin levels.

How does this all fit with suggestions that shift workers have higher rates. If cancer proliferates at night / sleep would one not expect to see lower levels in shift workers?

And which immune system or both, learned body wide, or innate cellular.

Is sleep not a repair mode of some sort?

If there is additional cancer growth at night / sleep have we somehow upset the balances in the repair system - back to fat intake balances?

So many questions.

RB

[heblaj01]

R.B.
Here is a curious study where the experimental drug TNP-470 is more beneficial in day time than at night for mice. This is opposite the case of humans described in the first post of this thread.
However mice being nocturnal animals could explain the difference in optimum timing.

http://jpet.aspetjournals.org/cgi/content/full/304/2/669

I wondered the same--and have been taking Arimidex at bedtime over the past 4 years and so far so good--dx'd 3/01 w/3 to 4 different types of very aggressive b.c. (pleomorphic invasive lobular, rare presentation of IBC (in nipple only w/Pagetian spread), and high grade dcis with extensive comedo necrosis), er+, her2+, 9 of 12 pos. nodes not matted together (but first CT scan report indicated that there appeared to be remaining lymph nodes that WERE matted together, elevated tumor markers, extensive lymphovascular invasion, and extracapsular spread.
Tx--bilateral mastectomy, chemo (4 AC), rads (25 treatments w/out boost), more chemo--2 Taxol and 2 Taxotere w/weekly Herceptin starting w/first taxane--for 1 year, followed by complete hysterectomy/oopherectomy. Other treatments--beta seron (for m.s. for past 11 yrs), Doxycycline and Celebrex--started after hysterectomy (a few mos. after becoming hypothyroid)--Celebrex -- initially 100 mg--twice/day, then after a month or two it was increased to 200 mg/twice/day, then 9 mos. later it was increased to 400 mg/twice/day and Lovastatin was added.

[heblaj01]

Kaye301,

I am glad you may benefit from optimum timing of Arimidex. It would be interesting to find out if others are doing likewise with their daily pills.
I am curious about why you are also taking Doxycycline.
Is it off label for bone density or for reactive arthritis or as anti agiogenesis agent or simply as an antibiotic for infection?

[heblaj01]

http://cancerres.aacrjournals.org/cg...ull/63/21/7277
A Molecular Mechanism Regulating Circadian Expression of Vascular Endothelial Growth Factor in Tumor Cells1

In this article the important cancer growth factor VEGF is shown to be at higher levels in mice tumours screened during daylight time compaired to night time.
It also has been shown in other mice experiments that some anticancer drugs are more effective if given during daylight time.
Optimum temporal control of VEGF (for instance with antiangiogenesis treatments) may thus provide one explanation of the validity of chronotherapy.

Since mice are nocturnal animals the reverse temporal effect may be seen in humans for whom night time treatments of VEGF may sometimes in the future be proven to be more effective (if the treatment drug has to be administered at least once a day).
Among the candidates for this type of chronotherapy are the chemo drugs (such as Cyclophosphamide) taken as a daily low dose pill in so called metronomic treatments where their antiangiogenesis properties are exploited as opposed to their cytotoxic properties in high dose regimens.

For instance in this clinical trial on ovarian cancer using daily Cyclophosphamide pills & weekly Avastin I.V.'s (an other antiangiogenesis drug), one can speculate that if the pills had been taken at night the outcomes might have been even better.
http://www.csmc.edu/pdf/WCRI-ASCO-Av...stin%20pill%22

TARGETED CANCER DRUG COMBINED WITH A PILL FORM OF LOW-DOSE
CHEMOTHERAPY FOUND TO SHRINK TUMORS AND SLOW PROGRESSION OFRECURRENT OVARIAN CANCER