Combination therapy

Combination therapy or polytherapy is therapy that uses more than one medication or modality (versus monotherapy, which is
any therapy taken alone). Typically, these terms refer to using multiple therapies to treat a single disease, and often all the therapies
are pharmaceutical (although it can also involve non-medical therapy, such as the combination of medications and talk therapy to
treat depression). 'Pharmaceutical' combination therapy may be achieved by prescribing/administering separate drugs, or, where
available, dosage forms that contain more than oneactive ingredient (such as fixed-dose combinations).

Polypharmacy is a related term, referring to the use of multiple medications (without regard to whether they are for the same or
separate conditions/diseases). Sometimes "polymedicine" is used to refer to pharmaceutical combination therapy. Most of these kinds
of terms lack a universally consistent definition, so caution and clarification are often advisable.

Contents
Uses for combination therapy
Combination therapy in oncology
Contrast to monotherapy
See also
References

Uses for combination therapy

Conditions treated with combination therapy include tuberculosis, leprosy, cancer, malaria, and HIV/AIDS. One major benefit of
combination therapies is that they reduce development of drug resistance, since a pathogen or tumor is less likely to have resistance
to multiple drugs simultaneously. Artemisinin-based monotherapies for malaria are explicitly discouraged to avoid the problem of
developing resistance to the newer treatment.

Combination therapy may seem costlier than monotherapy in the short term, but when used appropriately, it causes significant
savings: lower treatment failure rate, lower case-fatality ratios, fewer side-effects than monotherapy, slower development of
[1]
resistance and consequently, less money needed for the development of new drugs.

Combination therapy in oncology

Combination therapy has gained momentum in oncology in recent years, with various studies demonstrating higher response rates
with combinations of drugs when compared to monotherapies,[2][3] and the FDA recently approving therapeutic combination
regimens that demonstrated superior safety and efficacy to monotherapies.[4] In a recent study about solid cancers, Martin Nowak,
Bert Vogelstein, and colleagues showed that in most clinical cases combination therapies will be needed to avoid the evolution of
resistance to targeted drugs. Furthermore, they find that the sequential administration of multiple targeted drugs precludes any chance
[1]
for cure — even when there are no possible mutations that can confer cross-resistance to both drugs.

Various systems biology methods have been utilized to discover combination therapies to overcome drug resistance in select cancer
types.[5][6] Recent precision medicine approaches have focused on targeting multiple biomarkers found in individual tumors using
combinations of drugs.[7] However, with 300 FDA-approved cancer drugs on the market, there almost 45,000 possible two-drug
combinations and almost 4.5 million three-drug combinations for to choose from.[8] This level of complexity is one of the primary
.[7]
impediments to the growth of combination therapy in oncology
 .[9]
The National Cancer Institutehas recently highlighted combination therapy as a top research priority in oncology

Contrast to monotherapy
Monotherapy can be applied to any therapeutic approach, but it is most commonly used to describe the use of a single medication.
Normally, monotherapy is selected because a single medication is adequate to treat the medical condition. However, monotherapies
may also be used because ofunwanted side effects or dangerous drug interactions.[10]

See also
Polypill, a medication which contains a combination of multiple active ingredients
Drug combination database.covers information on more than 1300 drug combinations in either clinical use or
different testing stages.
Perturbation biology method for the discovery of anti-resistance drug combinations with network pharmacology
.

References
1. Bozic; Reiter; Allen; et al. (June 25, 2013)."Evolutionary dynamics of cancer in response to targeted combination
therapy" (https://dx.doi.org/10.7554/eLife.00747). eLife. 2:e00747. doi:10.7554/eLife.00747 (https://doi.org/10.7554%
2FeLife.00747).
2. Janku, Filip; Hong, David S.; Fu, Siqing; Piha-Paul, Sarina A.; Naing, Aung; Falchook, Gerald S.;simberidou,
T
Apostolia M.; Stepanek, Vanda M.; Moulder, Stacy L. (2014-01-30)."Assessing PIK3CA and PTEN in early-phase
trials with PI3K/AKT/mTOR inhibitors" (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409143). Cell Reports. 6 (2):
377–387. doi:10.1016/j.celrep.2013.12.035(https://doi.org/10.1016%2Fj.celrep.2013.12.035) . ISSN 2211-1247 (http
s://www.worldcat.org/issn/2211-1247). PMC 4409143 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4409143) .
PMID 24440717 (https://www.ncbi.nlm.nih.gov/pubmed/24440717).
3. Musgrove, Elizabeth A.; Caldon, C. Elizabeth; Barraclough, Jane; Stone, Andrew; Sutherland, Robert L. (2011-07-
07). "Cyclin D as a therapeutic target in cancer"(https://www.ncbi.nlm.nih.gov/pubmed/21734724). Nature Reviews.
Cancer. 11 (8): 558–572. doi:10.1038/nrc3090 (https://doi.org/10.1038%2Fnrc3090). ISSN 1474-1768 (https://www.
worldcat.org/issn/1474-1768). PMID 21734724 (https://www.ncbi.nlm.nih.gov/pubmed/21734724).
4. "Novartis receives FDA approval for first-of-its-kind Kisqali® Femara® Co-Pack for initial treatment of HR+/HER2-
advanced or metastatic breast cancer | Novartis US"(https://www.pharma.us.novartis.com/news/media-releases/nov
artis-receives-fda-approval-first-its-kind-kisqalir-femarar-co-pack-initial)
. www.pharma.us.novartis.com. Retrieved
2017-10-03.
5. Korkut, A; Wang, W; Demir, E; Aksoy, BA; Jing, X; Molinelli, EJ; Babur, Ö; Bemis, DL; Onur Sumer, S; Solit, DB;
Pratilas, CA; Sander, C (18 August 2015). "Perturbation biology nominates upstream-downstream drug combinations
in RAF inhibitor resistant melanoma cells"(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4539601). eLife. 4.
doi:10.7554/elife.04640 (https://doi.org/10.7554%2Felife.04640). PMC 4539601 (https://www.ncbi.nlm.nih.gov/pmc/a
rticles/PMC4539601) . PMID 26284497 (https://www.ncbi.nlm.nih.gov/pubmed/26284497).
6. Lee, MJ; Ye, AS; Gardino, AK; Heijink, AM; Sorger, PK; MacBeath, G; Yaffe, MB (11 May 2012)."Sequential
application of anticancer drugs enhances cell death by rewiring apoptotic signaling networks"
(https://www.ncbi.nlm.n
ih.gov/pmc/articles/PMC3501264). Cell. 149 (4): 780–94. doi:10.1016/j.cell.2012.03.031(https://doi.org/10.1016%2F
j.cell.2012.03.031). PMC 3501264 (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3501264) . PMID 22579283 (http
s://www.ncbi.nlm.nih.gov/pubmed/22579283).
7. "Drug Combinations to Overcome Treatment Resistance" (https://www.cancer.gov/about-cancer/treatment/research/
drug-combo-resistance). National Cancer Institute. Retrieved 2017-10-03.
8. Culjat, M (2017-05-11)."By the Numbers: Combination Therapy in Oncology | CureMatch"(https://www.curematch.c
om/media/blog-posts/numbers-combination-therapy-oncology/)
. CureMatch Blog. Retrieved 2017-10-03.
9. "Combination Therapies for Cancer - Annual Plan"(https://www.cancer.gov/about-nci/budget/plan/treating/combining
-therapies). National Cancer Institute. Retrieved 2017-10-03.
10. "Glossary" (http://www.epilepsy.uhhs.com/glossary.htm). Retrieved 2008-04-02. "Monotherapy: The treatment of
epilepsy with a single medication rather than a combination. Monotherapy has advantages over combining
 medications in many patients, including absence of drug-drug interactions, fewer side fects,
ef simpler dosing, and
lower cost. However, not all patients can be controlled with monotherapy."

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