Adjuncts to Chemotherapy

The ubiquitous distribution of both MTs and stress proteins may be exploited in cancer therapy regimens. MT may serve as an adjunct in cancer chemotherapy (Imura et al. 1991 Cherian et al. 1994). The selective induction of MT by bismuth in noncancer cells protects these cells from harmful side effects of a number of chemotherapeutics, including alkylating agents, antimetabolites, and mitotic inhibitors, but does not interfere with the efficacy of these compounds. Conversely, the presence of MT in tumors may act as a multidrug resistance factor in cancer chemotherapy (Cherian et al. 1994). While the role of stress proteins is not clearly defined, hyperthermia potentiates the antitumor effects of chemotherapeutics and radiotherapy (Nover 1991). 

While MTs are structurally and mechanistically distinct from the classical stress proteins, MTs share many similar functions with this broad class of proteins. MT appears to be a stress protein, based on similarities with stress proteins, with regard to ubiquitous distribution, high evolutionary conservation, protective functions, and gene regulation properties. 

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Grigg A, Solal-Celigny P, Hoskin P, et al. Open-label, randomized study of pegfilgrastim vs. daily filgrastim as an adjunct to chemotherapy in elderly patients with non-Hodgkirfs lymphoma. Leak. Lymphoma 2003 44 1503-1508. 

The MDR transporter is of importance in drug resistance in antiprotozoal and anticancer chemotherapy and hence compounds that inhibit this transporter are potentially very useful as adjuncts to chemotherapy to overcome such drug resistance (Table 13.7). This chapter also deals with numerous plant-derived compounds that inhibit various other enzymes (Table 13.8). 

Sargramostim (r-HuGM-CSF) Leukine (Berlex) Myeloid reconstitution after bone marrow transplantation bone marrow transplant failure adjunct to chemotherapy in AML peripheral blood progenitor cell transplant... 

The mistletoe lectins inhibited the growth of multidrug-resistant human colon cancer line HT 29 (mdr) in vitro Numerous studies have reported immunostimulatoiy and proapoptotic effects for mistletoe extracts, preparations, and components. The mistletoe extracts and preparations also significantly inhibited carcinogenesis and metastatis. Animal studies have shown that mistletoe preparations suppressed side effects when used as an adjunct to chemotherapy and radiation therapy. ... 

Results of this trial clearly encourage further research of microspheres as an adjunct to chemotherapy and other therapeutic modalities in metastatic breast cancer. 

LA. Infusion. In 1961, Byron et al. reported on their experience with intraarterial infusion of ten patients with bladder cancer who failed to respond. The use of intraarterial chemotherapy was reported by Nevin and Hoffman (1975), who surgically implanted catheters into each internal iliac artery. 5-Fluoroura-cil was infused for 10 days and then every other week for 3 months when it was given as an adjunct to chemotherapy. Regression of local disease was seen in six of ten patients. A mean survival time of 25 months was noted in the complete responders. Fourteen of 28 patients responded but, because of the dosage and myelosuppression, local irritation was significant. 

Granulocyte colony stimulating factor 127 amino acids E. coll Adjunct to cancer chemotherapy Approved for sale By stimulating white blood cell formation, aids recovery... 

Over 70 randomized trials comparing radiation to chemoradiotherapy have been completed in the hopes of ascertaining the absolute benefits of chemotherapy when used as an adjunct to radiotherapy in local control, overall survival, and relapse-free survival. However, these studies often involved small cohorts. As such, meta-analyses were created to assess a larger patient population and to help determine the absolute benefits of the addition of chemotherapy (69-71). 

Haffty BG, Son YH, Papac R, et al. Chemotherapy as an adjunct to radiation in the treatment of squamous cell carcinoma of the head and neck results of the Yale Mitomycin Randomized Trials. J Clin Oncol 1997 15 268-276. 

Anemia. Testosterone and similar compounds are potent stimulators of erythropoietin synthesis from the kidneys and other tissues.109 Erythropoietin, in turn, stimulates production of red blood cell synthesis in bone marrow. Human erythropoietin, however, can now be synthesized using recombinant DNA techniques. Hence, various types of anemia that occur secondary to renal disease, cancer chemotherapy, and so forth are usually treated directly with recombinant erythropoietin.109 Nonetheless, androgens may be used as an adjunct to erythropoietin and other drugs to stimulate red blood cell production in certain patients with severe or recalcitrant anemia.10... 

P-gp Inhibition as an Adjunct to Treating Chemotherapy-Resistant Cancers... 

Cancer Chemotherapy. As if they did not already suffer enough, cancer patients undergoing chemotherapy experience several disconcerting and unpleasant side effects of treatment such as vomiting and nausea. By chance, one such patient happened to use marihuana after receiving chemotherapy and he found that the vomiting he usually experienced was alleviated. He reported this effect to his doctors, and subsequent testing at the Harvard Medical School proved so satisfactory that marihuana has become a routine adjunct to cancer chemotherapy at some hospitals. 

Leukocytosis is a normal host defense to infection and is an important adjunct to antimicrobial therapy. Unfortunately, bacterial infection is a common complication of neutropenia from cancer chemotherapy. These patients are incapable of increasing their WBCs in response to infection. In fact, susceptibility to infection in these patients is highly dependent on their WBC status. Patients with neutrophil counts of less than 500 cells/mm are at high risk for the development of bacterial or fungal infections. The absence of leukocytosis also occurs in the elderly and in severe cases of sepsis. ... 

Geissler K, Roller E, Hubmann E, et al. Granulocyte colony-stimulating factor as an adjunct to induction chemotherapy for adult acute lymphoblastic leukemia—a randomized Phase-III study. Blood 1997 90 590-596. 

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