"When Should Chemotherapy be Considered?" TUMOR TIDBITS, A BIWEEKLY EMAIL NEWSLETTER FROM GULF COAST VETERINARY ONCOLOGY Number 70; September 20, 2002. ======================================================================= THIS WEEK'S TUMOR TIDBIT: WHEN SHOULD CHEMOTHERAPY BE CONSIDERED? ======================================================================= For this week's Tidbit, I've included an email conversation that occurred recently and then included some biological information afterwards..... A RECENT QUESTION OVER THE INTERNET: "Hi Dr. Hahn, I'm writing to you because my 18 year old cat has just been diagnosed with an abdominal tumour that came back positive for cancer. The cytology report read that the site of origin could not be determined however, pancreatic carcinoma is given primary consideration. I am not inclined to put her through surgery at this point - the sonogram shows there may be some intestinal involvement. In the meantime, no one is offering any other treatment modalities instead of surgery. I want to keep her home with me, and as comfortable as I can, but I don't want her to suffer or be in pain. If the cancer is surgically removed, it's likely that it will come back. Any advice? Is chemotherapy helpful? Thank you so much in advance for your help!" MY ANSWER: "I wish I could give you the "right" answer over the internet. It's always hard to give advice over the internet and oftentimes there's information that's helpful that only an in-person physical exam can provide. However, in general, our approach to managing a cat with an abdominal mass is to always determine if surgery is possible. Less disease is always best and allows for more options to maintain remission or control of the disease. However, if surgery cannot be done or should not be done (for any reason), then the role of chemotherapy is to manage the disease without affecting quality of life. If this provides additional quantity of time, that's great too. Chemotherapy can be given even if the textbooks say the prognosis is poor. Sure, it's poor because it will never cure the cancer, but if it reduces tumor burden without causing signficant side effects to the pet (a matter of dose selection - giving more drug may kill more cancer but cause more side effects, less drug hurts less but kills less cancer) then quality of life should happen. Pain control and quality control can be as, if not more, important than cancer control. So, trust your heart. It's not important whether or not the cancer can be treated, it's more important to decide on what's best for the pet's quality of life. If what is best also includes surgery, chemotherapy, etc, then that should feel right to you and your pet. Talk to your veterinarian, and possibly consider talking to a local or regional internist or oncologist (try www.acvim.org). That's the best I can offer." WHEN SHOULD CHEMOTHERAPY BE CONSIDERED? When considering the use of chemotherapy in the tumor-bearing patient, the approach to therapy will vary greatly depending on the therapeutic intent. Will the therapeutic goal be cure or palliation? It is important to determine the goal clearly at the outset. Cure is the ideal outcome, but is not necessarily realistic in most cases or likely to be achieved unless it is the initial intent. If cure is the intended outcome, aggressive therapy may provide substantial long-term benefit and a relatively high level of short-term toxicity may be justified. More commonly, the accepted goal of cancer therapy in veterinary medicine is palliation. Toxicity to chemotherapy is minimized in an attempt to prolong an acceptable quality of life. Although localized primary tumors which have a minimal risk for metastasis are most commonly treated with surgery and/or radiation, chemotherapy may occasionally be used instead of or in addition to standard local therapy. Systemic chemotherapy is also indicated following local treatment for adjunctive therapy in tumors that are commonly widespread or demonstrate a high rate of metastatic behavior (e.g., osteosarcoma, oral melanoma). TUMOR GROWTH AND RESPONSE TO CHEMOTHERAPY An understanding of cell growth, the biologic behavior of tumors, and the metastatic pattern of specific tumor types are essential prior to formulating a treatment plan. The phases of the cell cycle are S, in which new DNA is synthesized, gap G1, a period of RNA and protein synthesis, M, when the cell undergoes mitosis, and a second gap, G2. The duration of each phase varies for different cell types. Resting cells, G0, may retain the capacity to divide upon proper stimulation. Normal and neo astic cell populations are composed of both proliferating and resting cells; the proportion and the rate of cell death vary with the tissue type. Growth fraction refers to the proportion of a population of cells, which is actively proliferating, in contrast to those that are viable but quiescent. This concept must be distinguished from growth rate, which refers to the increase in size of the tumor over time. It is helpful to consider the rate of growth of a tumor more in terms of doubling time than in terms of size per time. Doubling time refers to the time required for doubling of cell number, which is clinically evident as volume. Some tumors are anatomically difficult to characterize, however most can be assumed to be roughly spherical for purposes of calculation. The smallest clinically detectable tumor generally has a mass of 1g, about 1 cm diameter and contains approximately 109 cells. If a tumor is assumed to have originated from a single cell, then it has already undergone 30 doublings by the time it is clinically detected. To increase in size to 1 kg theoretically takes only another ten doublings, assuming that all cells survive. Thus the majority of the lifespan of a tumor is probably spent in the subclinical phase. Depending on the growth fraction and the rate of cell death, normal cell growth is classically thought of as an exponential phenomenon in which the rate of doubling of the population remains fixed over time. Tumor cell populations, however, tend to adhere more closely to Gompertzian kinetics, meaning that the doubling time tends to increase exponentially over time then reach a plateau phase. The plateau phase is most likely due to a decrease in the growth fraction due to hypoxia, depletion of nutritional factors, and an increase in the rate of cell death rather than an increase in the length of the cell cycle. In general, the higher the growth fraction of a population of cells, the more chemosensitive they are expected to be. This explains why the most common side effects of chemotherapy are gastrointestinal disturbances and bone marrow suppression, since these populations are constantly proliferating. Likewise, a tumor that is reaching the plateau phase of the growth curve due to hypoxia and poor cell nutrition will be more chemoresistant than one in the exponential or linear phase. Whether palliation or cure is the therapeutic goal, remission of tumors is desirable. Complete remission is defined as an inability to detect clinical evidence of tumor. This does not mean that all tumor cells have been removed. The remaining cells are a source of potential relapse or recurrence of gross tumor. When relapse occurs during chemotherapy, it implies that the tumor is resistant to the agents being given. Once your goal is set, cure or palliation, then begin to explore the options (surgical, radiation, drugs) best for the pet. ======================================================================= SUGGESTED READING Veterinary Oncology, From "The Practical Veterinarian Series". By Hahn KA. Butterworth-Heinemann Press, 2002. ======================================================================= We hope this info helps and don't hesitate to call us Gulf Coast Veterinary Oncology! Kevin A. Hahn, DVM, Phd, Diplomate ACVIM (Oncology), drhahn@gcvs.com Janet K. Carreras, VMD, Residency Completed and Certification Examination Passed, ACVIM (Oncology), drcarreras@gcvs.com Glen K. King, DVM, MS, Diplomate ACVR (Radiology & Radiation Therapy), drking@gcvs.com Gulf Coast Veterinary Diagnostic Imaging & Oncology 1111 West Loop South, Suite 150, Houston, TX 77027 P: 713.693.1166 F: 713.693.1167 W: www.gcvs.com