Cancer response

Leichman CG, Lenz HJ, Leichman L et al. Quantitation of intratumoral thymidylate synthase expression predicts for disseminated colorectal cancer response and resistance to protracted-infusion fluoro-uracil and weekly leucovorin. J Clin Oncol 1997 15 3223-3229. 

Baseline laboratory tests should include complete blood cell count, prothrombin time, activated partial thromboplastin time, liver and renal function tests, and serum carcinoembryonic antigen (CEA). Serum CEA can serve as a marker for monitoring colorectal cancer response to treatment, but it is too insensitive and nonspecific to be used as a screening test for early-stage colorectal cancer. 

Lotze, M.T. et al., High-dose recombinant interleukin 2 in the treatment of patients with disseminated cancer. Responses, treatment-related morbidity, and histologic findings, JAMA, 256, 3117, 1986. 

Chemotherapeutic agents that have significant cancer response when combined with hyperthermia (up to 43°C) include doxorubicin, melphalan, mitomycin C (MMC), mitoxantrone, gemcitabine, etoposide, and especially the platinum-based agents carboplatin and oxaliplatin (Mohamed et al., 2003 Sugarbaker et al., 2005). Agents that do not work well with hyperthermia include irinotecan, paclitaxel, docetaxel, 5-fluorouracil, and floxuridine (Mohamed et al., 2003 Sugarbaker et al., 2005). 

Symmans W, Volm M, Shapiro R, et al. Paclitaxel-induced apoptosis and mitotic arrest assessed by serial needle aspiration implications for early prediction of breast cancer response to neoadjuvant treatment. Clin Cancer Res 2000 6 4610-4617. 

Cisplatin was first used to treat advanced cervical cancer shortly after the drug was introduced into clinical practice in the early 1970s. Although cisplatin continues to be one of the most active agents against cervical cancer, response rates are less than 30% for patients with recurrent or metastatic disease, and complete responses are rare and usually of short duration (14). 

Horwitz RI, Feinstein AR. Estrogens and endometrial cancer. Responses to arguments and current status of an epidemiologic controversy. Am J Med 1986 81(3) 503-7. 

Modlich O, Prisack HB, Munnes M, Audretsch W, Bojar H. Predictors of primary breast cancers responsiveness to preoperative epirubicin/cyclophosphamide-based chemotherapy Translation of microarray data into clinically useful predictive signatures. J Transl Med 2005 3 32. 

There is strong evidence that the key precursor events that precede the cancer response in animals are anticipated to occur in humans and progress to tumors, based on available biological information. 

While combination chemotherapy and high-dose therapy (with or without stem cell transplantation) can increase cancer response rates, they generally increase toxicity significantly and sometimes in unanticipated ways when drugs interact with each other. Hence, the toxicity of each combination chemotherapy protocol and each high-dose therapy protocol must be considered individually. 

Figure 4 Representative examples of U- (or J-) shaped dose-response relationships of cancer responses induced by various radiation sources. The asterisks indicate statistically significant data ( = P < 0.05, = P < 0.01). Absence of statistical significance denotes studies that...

Several randomized trials have demonstrated that leuprolide and goserelin are effective agents when used alone in patients with advanced prostate cancer. Response rates around 80% have been reported, with a lower incidence of adverse effects compared with estrogens. There are no direct comparative trials of the currently available LH-RH agonists or the dosage formulations, but a recent meta-analysis reported that there is no difference in efficacy or toxicity between leuprolide and goserelin. Therefore the choice between the two is usually made based on cost and patient and physician preference for a dosing schedule. 

Shapiro JD, Millward MJ, Rischin D, et al. Activity of gemcitabine in patients with advanced ovarian cancer Responses seen following platinum 91. 

This chapter aims to discuss of cancer risks and hormesis within the U.S. regulatory risk assessment practices, which legally require the characterization of causal relations between exposures or doses and responses to quantify the probability of cancer response. Causal reasoning characterizes environmental decision-making (EPA 2005 statement in square brackets added) because ... 

In practice, in the absence of positive human epidemiological studies, the cancer response in the rat or mouse by a specific chemical is considered to be definitive for the identifying the chemical as a presumptive human carcinogen and for determining the relative carcinogenic potency in the exposed individuals. The exceptions to this practice are situations where it can be shown that the rodent carcinogenicity occurs by a mechanism(s) that is not operative in humans. 

Integration of the results from the above two steps to determine the cancer response (P(d)) during mixed exposures, as follows P d) = q ss eD ssae... 

Jensen, E.V., Block, G.E., Smith, S., Kyser, K. and DeSombre, E.R. (1971) Estrogen receptors and breast cancer response to adrenalectomy. Journal of the National Cancer Institute Monographs, 34, 55-70. 

Worden FP, Kumar B, Lee JS, et al. Chemoselection as a strategy for organ preservation in advanced oropharynx cancer response and survival positively associated with HPV16 copy number. / Clin Oncol. 2008 26(19) 3138-3146. 

Thymidylate synthase Methotrexate Leukemia response, colorectal cancer response... 

Seibert RM, Ramsey CR, Hines JW et al (2007) A model for predicting lung cancer response to therapy. Int J Radiat Oncol Biol Phys 67 601-609... 

The mode(s) of carcinogenic action and associated key events have been identified in animals, and The key events that precede the cancer response in animals have been observed in the human population(s) that also shows evidence of an association of exposure to the agent with cancer. 

The combination of RA plus IFN plus subcutaneous interleukin-2 plus 5-fluorouracil was given to 44 patients with progressive metastatic RCC and resulted in a major response rate of 44%, including six complete responses. Responding cancers included lung, liver and adrenal cancers. Responses were durable in 19 of the 20 responding cases and prolonged stabilization of disease occurred in 21 patients (47%). Another study of RA plus IFN in 19 patients with metastatic disease that was refractory to IFN, interleukin-2 and chemotherapy achieved a major response rate of 21% (4/19) [27]. 

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