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Review Article Open Acc J of Toxicol Volume 2 Issue 5 - March 2018 Copyright © All rights are reserved by Afroze Alam DOI : 10.19080/OAJT.2018.02.555600 Treatment and Strategy Schemes: A Review

Afroze Alam1,5*, U Farooq2, Ruchi Singh1, VP Dubey1, Shailendra Kumar3, Rashmi Kumari1, Kamlesh Kumar Naik4, BD Tripathi1 and KL Dhar5 1Narayan Institute of Pharmacy, India 2Faculty of Dentistry, Taif University, Saudi Arabia 3Govt Pharmacy Institute, India 4Nandha College of Pharmacy, India 5Faculty of Pharmaceutical Sciences, Shoolini University, India Submission: November 03, 2017; Published: March 29, 2018 *Corresponding author: Afroze Alam, Narayan Institute of Pharmacy, Bihar, India, Tel: ; Fax: +91-1792308000; Email:

Abstract Chemotherapy treatments are used to inhibit vigorously growing malignant cells with anticancer agents. This type of may be used to and try a patient to produce palliative relief and symptomatic relaxation in the advance stages of . In general, chemotherapy is given in cyclic manners. Patients are administered with anticancer drug during regular weekly or bi-weekly sessions. After the completion of

effects of anticancer drugs. Generally, six or more chemotherapeutic cycles are needed in cancer patient and often a combined chemotherapy certain cyclic session, treatment is stopped for several fixed periods to allow the patient to rest and their body to re-establish from the toxic normal circumstances, such as those in the digestive tract, bone marrow and hair follicles. Combination chemotherapy is always preferred overwould traditional be preferred. , Anticancer such drugs as radiotherapy, are used to destroysurgery not or onlyother to cytotoxic specific cancer drugs. cell The but mechanism equally affect of action the normal of each cell therapy that developing is different under for

reviewinhibiting describes cell division the alternative and proliferation methods of that rapidly combine growing chemotherapy cell. Each withtreatment other hastreatment their specific strategies side have effects. been A explored large numbers in order of to treatment improve strategy are available to fight with cancer, depending upon the severity and stage of cancer, type of cancer, and the affected body parts. The

treatmentKeywords: selectivity, Chemotherapy; reduce Cytotoxic recurrence agents; and improve Radiotherapy; the quality Non-pharmacological of life of patients. treatment; Cell proliferation; Hypertheramia

Introduction meaning thereby is that chemotherapy also destroy cells that Chemotherapy literally means the use of chemicals in divide rapidly under normal circumstances: digestive tract, order to inhibit malignant cell or to the infectious agents of a cell in bone marrow and hair follicles. There is a most common disease such as micro-organism without much affecting the side effects observed during the period of chemotherapy host cells [1]. Therefore, the treatment can be broadly divided into two categories - cancer chemotherapy and antimicrobial tract), alopecia (hair loss) and myelosuppression (decreased chemotherapy. The drugs belong to these categories, are treatment: mucositis (inflammation of the lining of the digestive production of blood cells, hence also immunosuppression) [4]. different from the others as they are generally intended to kill or Most of the monoclonal are not indiscriminately inhibit the target organism and have no or minimal effect on host cytotoxic and act by targeting proteins that are over expressed cell [2]. Earlier, it was considered that the chemotherapeutic in cancer cells and essential for their proliferation [5]. This kind agents were restricted to synthetic compounds but, now a of treatments is generally referred as (distinct day many more natural products are marketed as potential from classical chemotherapy) is always administered together chemotherapeutic agents or antibiotics. The present status with traditional chemotherapeutic agents in cancer treatment demands that both the synthetically as well as naturally or regimen. Furthermore, in addition to the combined and targeted microbiologically produced drugs need to be included together. chemotherapy, some of the newer strategy have also been In traditional chemotherapy, all the anticancer drugs are explored particularly the use of light (phototherapy) and heat cytotoxic in nature to both cancer as well as normal cells [3],

Open Acc J of Toxicol. 2018; 2(5): OAJT.MS.ID.555600 (2018) 001 Open Access Journal of Toxicology

therapy is used. drugs that converted to cytotoxic agent only upon the exposure (hyperthermia) techniques. In some of the strategy where, the d) In combined chemotherapy, different dugs are having of light is called photo chemotherapy or different kinds of mechanism of action and their side [6]. effects. The most advantage of combined chemotherapy is to Treatment strategies minimize the chances of development of resistance to any one the drug. Also the drugs can be administered at lower Now a day, many strategies have been adapted to dose with minimal side effects and toxicity administered chemotherapeutic drugs. Chemotherapeutic drugs may be used with a curative purpose or it may be aimed to prong e) .Neoadjuvant chemotherapy is used prior to a local life. treatment such as , and is meant to shrink the primary tumor [9]. It is also used to a condition where a high a) Combined chemotherapy is the one kinds of treatment risk of micrometastatic disease observes. strategy where more one type of therapy can be adopted at a time to treat cancer, such as , surgery and/ f) This therapy (Neoadjuvant chemotherapy) can be used or hypertheremia. However, induction chemotherapy is used where there is a little a chance or evidence of cancer present

[7]. the cancerous cells that have proliferated to other part of the for the first time treatment of cancer with anticancer drug and also there is risk of recurrence. It is also beneficial to kill body [10]. b) Consolidation chemotherapy is generally given after remission in order to prolong the overall disease-free time g) Maintenance chemotherapy is one where a repeated and improve overall survival [8]. low-dose is used to treat for prolong remission.

h) Salvage chemotherapy is useful to simply decrease consolidation therapy but a different drug than induction tumor load and increase life expectancy [11] (Table 1). c) Intensification chemotherapy is identical to Table 1: Common combination chemotherapeutic regimen [1]. Cancer Type Drugs Acronym

Mustine, Vincristine, Procarbazine, Prednisolone MOPP Hodgkin’s Disease Doxorubicine, Bleomycine, Vinblastine, Dacarbazine ABVD

Cyclophsphamide, Methotraxate, 5-Fluorouracil CMF Breast Cancer Doxorubicine, Cyclophsphamide AC Germ Cell Tumor Bleomycin, Etopside, Cisplatin BEP Stomach Cancer Epirubicine, Capecetabine, Cisplatin EXC Epirubicine, Cisplatin, 5- Fluorouracil ECF Bladder Cancer Methotraxate, Vincristine, Doxorubicine, Cisplatin MVAC Non-Hodgkin’s Cyclophsphamide, Doxorubicine, Vincristine, Prednisolone CHOP Cyclophsphamide, Doxorubicine, Vincristine CAV 5- Fluorouracil, Folonic acid, Oxaliplatin FOLFOX

All the above chemotherapeutic regimens are given to anticancer drugs [13]. The intense toxicity observed with the the patient that may be capable of withstand the treatment. A administration of anticancer drugs is because of the cytotoxic patient can be able to continue the chemotherapy or whether the dose reduction is needed, for that a performance status is always rapidly growing or developing cell, tumor or normal. Targeted agent that targets non-specific cell. They can inhibit or kill any used as a measure. Because less cell death is observed in tumor therapies are directly involved to affect cellular proteins, which are responsible to produce abnormal cell growth [14]. the size of the tumor. Current chemotherapy regimens are used This shows that there is a need of the high dose to cancer cells with each treatment, doses repetitions are required to reduce with relatively low dose to others normal cells. Different type treatments limited by toxicity to the patient [12]. to treat in cyclic manners, with the duration and frequency of or even on a patient basis under targeted therapies. Moreover, Cytotoxic agents and targeted therapy of cancer can be treated by the use of specific type of proteins the side effects observed are relatively less as compare to the Targeted therapies are known to be a relatively new approach traditional anticancer drugs. Initially, the target therapies were supposed to be only selective for one protein. However, now many of the issues observed during the use of traditional for cancer treatment, and the therapy significantly overcome it is quite clear that one drug can bind in a specific range of How to cite this article: Afroze Alam, U Farooq, Ruchi Singh, VP Dubey, Shailendra Kumar, et al. Chemotherapy Treatment and Strategy Schemes: A 002 Review. Open Acc J of Toxicol. 2018;2(5): 555600. DOI: 10.19080/OAJT.2018.02.555600. Open Access Journal of Toxicology protein target [15]. An example target for targeted therapy is and death [22,23]. There are a number of other strategies that the protein produced by the Philadelphia chromosome, a genetic oncologists can use to regulate chemotherapy. lesion found commonly in chronic myelomonocytic . Targeted Therapy This fusion protein has activity that can be inhibited by a drug [16]. Chemotherapy Treatment Strategy Using Hyperthermia. Targeted therapies specifically target a protein or other moleculesHormone and Therapy have the benefit of reducing chemo side effects. In traditional chemotherapy, there is a major drawback of the lack of selectivity, leads to various side- effects, such as alopecia Activated hormone receptors change the way that a gene is (hair loss), blood disorder, fatigue, nausea and vomiting. So, there expressed. That means these receptors change the way that the is a need to explore other treatment strategy where application gene behaves, often stimulating cell growth. Hormone-sensitive of heat (Hyperthermia) is accompanied together with other cancer cells have extra hormone receptors [24]. in order to improve treatment selectivity, Dose-Dense Chemotherapy Dose-dense chemotherapy treatment refers to treatments has been observed that surgical removal of solid tumor generally reduce recurrence and improve the quality of life of patients. It that are timed to occur close together. If conventionally scheduled fails in total remission and therefore a combination therapy chemotherapy treatments are once every three weeks, the dose- must be accompanied by anticancer drugs with radiotherapy or dense schedule might be once every two weeks. This strategy is hyperthermia or targeted therapy etc. One new approach, which used for more advanced that are starting to spread [25]. along with other mode of chemotherapy. In the hyperthermia Combined Modality Chemotherapy may achieve these goals, is to the use of hyperthermia technique process a fractionated or continued dose is delivered at the target Combined modality simply means using more than one type site that can increase the sensitivity of tumor to chemotherapy, of therapy to treat the cancer. If the cancer is aggressive and at radiotherapy, and immune-based strategies stage 3, the treatment includes surgery, chemotherapy, radiation, [17]. However, this kind of new approach where the successful and then a year of Herceptin. application of hyperthermia (where heat is applied only at the tumor site) together with other chemotherapeutics has led to Palliative Chemotherapy Palliative therapy is treatment that is given to improve objective of hyperthermia is to make tumor cells more sensitive renewed interest in the field of modern chemotherapy. The major towards the therapeutic agents and facilitate drug release from reduce the tumor size to improve organ function, rather than to quality of life. The purpose of is to ease pain and thermo responsive nano carriers (usually below 43°C, referred eliminate the cancer altogether. While it is often thought of as a to as mild hyperthermia) or, at higher temperatures, directly long-term end-of-life strategy to provide comfort, palliative care inducing necrosis (above 43°C, referred to as thermal ablation) can also be a temporary addition to the treatment strategy at any [18]. Furthermore, cancer cells are more sensitive towards thermal environment than normal tissues between 42-45°C with a directly proportional relationship between tissue death and pointPhotodynamic in the process therapy to address (PDT) a quality-of-life issue [26]. the temperature or exposure time. The mechanism of action of It is a ternary treatment for cancer involving a photo hyperthermia is accompanied by various way where the cells or sensitizer, tissue oxygen, and light (often using . tissues leading to an enhanced antitumor response. In general, Photodynamic therapy can be used as treatment for basal cell hyperthermia inhibits cell functions, increase permeability and carcinoma (BCC) or lung cancer; PDT can also be useful in removing traces of malignant tissue after surgical removal of impending trans membrane transport proteins and cell surface large tumors [27]. modify fluidity, disrupt stability and shape of cell membrane, receptors [19]. Transfer of heat, away from tumor cells is directly Cancer immunotherapy refers to a diverse set of therapeutic proportional to the rate and volume of tumor perfusion [20], strategies designed to induce the patient’s own tissue compared to healthy tissue [21], enforcing selectivity of an against tumors include intravesical BCG and assuming that the process is more efficient in malignant to fight the tumor [28]. Contemporary methods for generating are supposed to be on protein as they undergo denaturation and other to induce an immune response in hyperthermia. However, the significant effects of hyperthermia immunotherapy for superficial bladder cancer, and use of and precipitation at temperature > 40°C. Although the effects and patients. on lipids are mostly reversible, but the effect on DNA where, double strand break and effect produced is substantial and Conclusion non-reversible. This basically inhibits many cellular processes There are so many types of treatments that this is not an such as cell cycle arrest, replication and synthesis of DNA and exhaustive listing of all the chemotherapy strategies available alters protein synthesis, leading to inhibition of cell proliferation

How to cite this article: Afroze Alam, U Farooq, Ruchi Singh, VP Dubey, Shailendra Kumar, et al. Chemotherapy Treatment and Strategy Schemes: A 003 Review. Open Acc J of Toxicol. 2018;2(5): 555600. DOI: 10.19080/OAJT.2018.02.555600. Open Access Journal of Toxicology

to oncologists. Research continues to develop new treatments 12. Green MR, Manikhas GM, Orlov S, Afanasyev B, Makhson AM, et al. and more strategies for using existing treatments. Further (2006) Abraxane®, a novel Cremophor®-free, albumin-bound particle form of paclitaxel for the treatment of advanced non-small-cell lung improvements of this treatment strategy will undoubtedly cancer. Ann Oncol 17(8): 1263-1268.

13. Cho K, Wang XU, Nie S, Shin DM (2008) Therapeutic nanoparticles for The strategy reported herein, i.e. based on modifying clinically involve the development of more efficient anticancer drugs. drug delivery in cancer. Clin Cancer Res 14(5): 1310-1316. approved drugs certainly holds promise. However, further 14. Peer D, Karp JM, Hong S, Farokhzad OC, Margalit R, et al. (2007) validation of all this approaches are still needed as authentic Nanocarriers as an emerging platform for cancer therapy. Nat strategy also display relevant therapeutic properties under Nanotechnol 2(12): 751-760. normal conditions and to determine whether it has advantages 15. Higueruelo AP, Jubb H, Blundell TL (2013) Protein–protein interactions over the well-established use of chemotherapeutics, some of as druggable targets: recent technological advances. Curr Opin which are progressing through clinical trials. Pharmacol 13(5): 791-796. 16. Fabian MA, Biggs WH, Treiber DK, Atteridge CE, Azimioara MD, et al. Acknowledgment (2005) A small molecule- interaction map for clinical kinase The authors thank to Narayan Institute of Pharmacy inhibitors. Nat Biotechnol 23(3): 329-336. and Faculty of Pharmaceutical Sciences, Shoolini University 17. Needham D, Dewhirst MW (2001) The development and testing of a BajholSolan H.P. (India) for providing research facilities. new temperature-sensitive drug delivery system for the treatment of solid tumors. Adv Drug Deliv Rev 53(3): 285-305.

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How to cite this article: Afroze Alam, U Farooq, Ruchi Singh, VP Dubey, Shailendra Kumar, et al. Chemotherapy Treatment and Strategy Schemes: A 004 Review. Open Acc J of Toxicol. 2018;2(5): 555600. DOI: 10.19080/OAJT.2018.02.555600. Open Access Journal of Toxicology

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How to cite this article: Afroze Alam, U Farooq, Ruchi Singh, VP Dubey, Shailendra Kumar, et al. Chemotherapy Treatment and Strategy Schemes: A 005 Review. Open Acc J of Toxicol. 2018;2(5): 555600. DOI: 10.19080/OAJT.2018.02.555600.