How To Choose a Chemotherapy Agent written and compiled by doctordee | Search LMS site |

Choosing a Chemotherapy Agent Some Drug Information Sites Circadian Rhythms
Choosing a Chemotherapy Agent
Your sarcoma oncologist will no doubt suggest a chemotherapy agent for you. 1.Your first action is to find the results of clinical trials for your LMS with this agent. ASCO and Pubmed/Medline will have the clinical trials listed. That will give you the general response rate and response interval, and the major toxicities of the drug. See the page "Access to Medical Information" on this website. 2. The only indication as to whether an agent will work for your individual tumor would be chemoresistance testing. This will tell you drugs that probably will NOT work, and eliminating the no-goers helps concentrate on those drugs that have a better chance of getting a response. Of course, de-differentiation/further mutations may make future tumor and mets more varied in their reactions. Read the webpage: "Testing your Tumor". Chemoresistance/chemosensitivity testing requires FRESH tissue shipped in special solution, sent immediately to the special labs that do it. 3. Sometimes specific tests can be done to indicate doxorubicin resistance, for instance, on the paraffin block... like the MDR gene. 4. DNA microarray or RNA microarray on the tumor will eventually tell us exactly what chemo will work on the tumor, and perhaps take ALL the guesswork out of it. However, I think we will still have the problem of nonhomogeneity, which means varied responses of some tumor cells. 5. ACTUALLY CHOOSING the chemo in this day and age would involve balancing the following factors: a. Any information available from 1, 2, 3, 4 above b. A comparison of side effects of the agent and physical conditions of the patient. For instance, doxorubicin would not be given to a person whose cardiac status or ejection fraction was not normal. They MIGHT chance Doxil, however, if they had no other choices. c. Some consideration of the primary site of the tumor. Gemcitabine+taxotere can work well on Uterine LMS, and so can Temodar. An LMS bone primary might respond to some osteosarcoma chemotherapy agents. d. Some consideration of financial situation. Doxorubicin is cheaper than Doxil. Dacarbazine is cheaper than Temodar. [HMO's are cost conscious. So are people without health insurance.] There are ways to get expensive drugs more cheaply from the manufacturers. See Getting Drugs Cheaply on this website. e. Whether to take high dose or normal dose or low dose [metronomic dosing] of the agent. High dose is usually expensive, because it requires Neupogen shots. For palliative care of stage iv LMS, often single agents are used, but not in high dosage. Each agent is used singly to get the most mileage out of it, with the least side effects, because there seems to be no proven survival advantage to using cocktails [except perhaps in very aggressive LMS, or in situations that are urgently life threatening]. f. There is a feeling that if a person's tumors responded to gemcitabine, that they might also respond to navelbine. g. If there is a clinical trial available and all other likely agents have been used, or don't work. Sometimes clinical trials use completely new agents which are not chemo agents but targeted molecular therapy -- like PS341 and CCI 779. h. Lists of side effects and package inserts can be obtained by doing a Google search online. Medline, Medscape, CancerBacup, CancerSource, and many other sites list information about cancer drug side effects, see the URLs below. i. Discuss all options, questions, and apprehensions with your sarcoma oncologist. j.This is a valuable resource for patients on chemo -- including new drug options and practical tips to combat or avoid fatigue, nausea, anemia, and other therapy-related side effects. WebMD Chemotherapy Information Before taking any chemotherapy or radiation therapy, notify your doctor of any of the following: a. If you are pregnant, breast feeding or planning children in the future, inform your doctor of this before treatment. This drug may cause birth defects if either the male or female is taking it at the time of conception or during pregnancy. Men and women who are taking this drug need to use some kind of birth control. However, do not use oral contraceptives without checking with your doctor. b. If you are thinking about wanting to have children in the future, be sure to discuss this with your doctor. Many chemotherapy drugs can cause sterility. c. If you have any of the following medical problems: chickenpox or exposure to chickenpox, gout, heart disease, congestive heart failure, shingles, kidney stones, liver disease. d. If you are taking any other prescription or over-the-counter drugs, including vitamins and herbals. Your prescription and nonprescription medications may interact with other drugs, causing a harmful effect. Certain foods or alcohol can also interact with drug products. Never begin taking a new medication, prescription or nonprescription, without asking your doctor or nurse if it will interact with alcohol, foods or other medications. Some drug products can cause drowsiness and may affect activities such as driving. While you are being treated with chemotherapy, and after you stop treatment, do not have any immunizations (vaccinations) without your doctor's okay. Try to avoid contact with people who have recently taken the oral polio vaccine. Check with your doctor about this. updated October 2003
Some Drug Information Sites
The Cancer.gov site is an NIH government site, Your Tax Dollars At Work. It is a very good site. What do do during Chemotherapy, from CancerNet is also on this site. Register for Medscape. It is free and you don't have to be a doctor. Medscape Drug Info Drug InfoNet was found by first going to the FDA's Oncology Tools site and clicking on Drug Info. There's much more at this site. CancerBacup is a good site with a lot of other information as well. As is CancerSource. The American Society of Clinical Oncologists [ASCO] maintains a good site with abstracts from papers presented at their conferences. These abstracts are often not available on Pubmed. For ASCO Searches you will have to go to the site and search the abstracts with keywords of the chemotherapy agent AND sarcoma. It is an excellent site for results of clinical trials of new agents. ASCO Abstract Search
Circadian Rhythms
Circadian rhythms, the cyclic variation of body metabolism during a 24 hour day, may be able to add to chemotherapy or radiation therapy effectiveness. "The circadian timing of surgery, anticancer drugs, radiation therapy, and biologic agents can result in improved toxicity profiles, tumor control, and host survival" See abstract below. Pubmed search term is also included. Pubmed search for circadian rhythms and cancer treatment Pubmed search for chronochemotherapy and cancer treatment Circadian chemotherapy for gynecological and genitourinary cancers. Kobayashi M, Wood PA, Hrushesky WJ. University of South Carolina School of Medicine, Columbia 29209, USA. "The circadian timing of surgery, anticancer drugs, radiation therapy, and biologic agents can result in improved toxicity profiles, tumor control, and host survival. Optimally timed cancer chemotherapy with doxorubicin or pirarubicin (06:00h) and cisplatin (18:00h) enhanced the control of advanced ovarian cancer while minimizing side effects, and increased the response rate in metastatic endometrial cancer. Therapy of metastatic bladder cancer with doxorubicin-cisplatin was made more tolerable by this same circadian approach resulting in a 57% objective response rate. This optimally timed therapy is also effective in the adjuvant setting, decreasing the expected frequency of metastasis from locally advanced bladder cancer. Circadian fluorodeoxyuridine (FUDR) continuous infusion (70% of the daily dose given between 15:00h and 21:00h) has been shown effective for metastatic renal cell carcinoma resulting in 29% objective response and stable disease of more than 1 yr duration in the majority of patients. Toxicity is reduced markedly when FUDR infusion is modulated to circadian rhythms." "...Biological agents such as interferon-alpha and IL-2 have shown low but effective disease control in Metastatic renal cell cancer, however, with much toxicity. Each of these cytokines shows circadian stage dependent toxicity and efficacy in model systems." "In summary, the timing of anthracycline, platinum, and fluoropyrimidine-based drug therapies during the 24 hour day is relevant to the toxic therapeutic ratio of these agents in the treatment of gynecologic and genitourinary cancers." Fetch PMID: 11962679 Last updated October 2003

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