http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db =PubMed&list_uids=12506180&dopt=Abstract Weekly high-dose calcitriol and docetaxel in metastatic androgen- independent prostate cancer. Beer TM, Eilers KM, Garzotto M, Egorin MJ, Lowe BA, Henner WD. Oregon Health & Science University and Portland VA Medical Center, Portland, OR 97239, USA. beert@ohsu.edu PURPOSE: To determine the safety and efficacy of weekly high-dose oral calcitriol (Rocaltrol, Roche Pharmaceuticals, Basel, Switzerland) and docetaxel (Taxotere, Aventis Pharmaceuticals, Bridgewater, NJ) in patients with metastatic androgen-independent prostate cancer (AIPC). PATIENTS AND METHODS: Thirty-seven patients were treated with oral calcitriol (0.5 micro g/kg) on day 1 followed by docetaxel (36 mg/m(2)) on day 2, repeated weekly for 6 weeks of an 8-week cycle. Patients maintained a reduced calcium diet and increased oral hydration. Prostate-specific antigen (PSA) response was the primary end point, which was defined as a 50% reduction in PSA level confirmed 4 weeks later. RESULTS: Thirty of 37 patients (81%; 95% confidence interval [CI], 68% to 94%) achieved a PSA response. Twenty-two patients (59%; 95% CI, 43% to 75%) had a confirmed > 75% reduction in PSA. Eight of the 15 patients with measurable disease (53%; 95% CI, 27% to 79%) had a confirmed partial response. Median time to progression was 11.4 months (95% CI, 8.7 to 14 months), and median survival was 19.5 months (95% CI, 15.3 months to incalculable). Overall survival at 1 year was 89% (95% CI, 74% to 95%). Treatment-related toxicity was generally similar to that expected with single-agent docetaxel. Pharmacokinetics of either calcitriol or docetaxel were not affected by the presence of its companion drug in an exploratory substudy. CONCLUSION: The combination of weekly oral high-dose calcitriol and weekly docetaxel is a well- tolerated regimen for AIPC. PSA and measurable disease response rates as well as time to progression and survival are promising when compared with contemporary phase II studies of single-agent docetaxel in AIPC. Further study of this regimen is warranted. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db =PubMed&list_uids=12475686&dopt=Abstract Fatal respiratory failure associated with treatment of prostate cancer using docetaxel and estramustine. Morris MJ, Santamauro J, Shia J, Schwartz L, Vander Els N, Kelly K, Scher H. Genitourinary Oncology Service, Department of Medicine, Memorial Sloan- Kettering Cancer Center and Cornell University Weill Medical College, New York, New York, USA. Chemotherapy that targets microtubular trafficking induces responses in most patients with prostate cancer. One regimen under investigation is the combination of docetaxel and estramustine. We report on 2 patients with androgen-independent disease who received continuous weekly docetaxel and estramustine and who died of irreversible respiratory failure. The clinical, pathologic, and radiographic data support drug toxicity as the likely etiology. Inclusive of these patients, only 17 cases (10 fatal) of acute pulmonary toxicity using docetaxel have been reported, despite its wide use. We recommend that patients receiving weekly docetaxel, with or without estramustine, have frequent treatment breaks and be evaluated with computed tomography of the chest every 8 weeks. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db =PubMed&list_uids=12423438&dopt=Abstract Docetaxel-induced nail dystrophy. Nicolopoulos J, Howard A. Department of Dermatology, Royal Melbourne Hospital, Melbourne, Victoria, Australia. A 73-year-old man with metastatic prostate cancer treated with weekly docetaxel chemotherapy for 5 months developed an acute nail dystrophy restricted to the fingernails. This was characterized by onycholysis, subungual haemorrhage and acute paronychia, progressing to a subungual abscess of the right index finger. Nail bed hyperaemia and haemosiderin- like nail bed discoloration were present. Nail plate avulsion was performed to decompress the acutely painful subungual abscess. The right thumb, middle finger and left index finger demonstrated early, proximal white subungual collections of pus obscuring the lunula (onychophosis). Central nail plate fenestrations with a surgical drill led to exudation of purulent material. Cultures of the subungual abscess material yielded mixed organisms, possibly related to administration of flucloxacillin for 1 week prior to presentation. The patient completed a further two courses of docetaxel without sequelae, and the nail dystrophy appears to be resolving. Docetaxel-induced nail changes are a common adverse effect, occurring in 30-40% of patients. Mild changes do not usually warrant the discontinuation of treatment. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db =PubMed&list_uids=12222966&dopt=Abstract Survival of docetaxel-resistant prostate cancer cells in vitro depends on phenotype alterations and continuity of drug exposure. Makarovskiy AN, Siryaporn E, Hixson DC, Akerley W. Department of Medical Oncology, Rhode Island Hospital/Brown University School of Medicine, Providence 02903, USA. We evaluated in vitro the effect of paclitaxel and docetaxel on PC-3 and DU-145 prostate cancer cell lines to understand better the downstream events in drug-induced tumor cell death. Taxane treatments of DU-145 cells induced rapid cell death by apoptosis, but in PC-3 cells, treatments achieved growth arrest, followed by extensive karyokinesis resulting in multinucleation, giant-cell formation and delayed cell death. To determine if the giant multinucleated cells were able to produce proliferating and drug-resistant survivors, we first delineated the kinetics of drug activity and cytotoxic dose range. Analysis of both lines by colorimetric and cell viability assays demonstrated improved cytotoxicity of taxanes applied continuously. Selected doses and schedules of docetaxel were used to induce giant multinucleated cells that gave rise to docetaxel-resistant survivors, which remained sensitive to paclitaxel and other chemotherapeutics. Growth and morphology of the recovered clones was similar to parental cells. The resistant phenotype of these clones determined by immunofluorescence and immunoblot was associated with transient expression of the beta-tubulin i.v. isoform and was independent of P-glycoprotein, bcl-2 and bcl-xL. Resistant clones will be useful to model progression of resistance to taxanes and to identify unknown and clinically important molecular mechanisms of cell death and resistance. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db =PubMed&list_uids=12198636&dopt=Abstract Chemotherapy for androgen-independent prostate cancer. Petrylak DP. College of Physicians and Surgeons of Columbia University, Columbia- Presbyterian Medical Center, New York, NY 10032-3789, USA. While men with metastatic prostate cancer frequently show a good initial response to androgen ablation, few options have been available for progressive hormone-refractory prostate cancer, and survival following chemotherapy has not exceeded 9 to 12 months. The combination of prednisone and mitoxantrone has significant palliative effects on bone pain but does not extend survival. The combination of estramustine phosphate (EMP) with the taxanes paclitaxel or docetaxel produces greater than additive cytotoxicity in vivo, and phase I and II studies of taxane-based therapy demonstrate improved survival in hormone- refractory prostate cancer compared to historical controls. Docetaxel appears to have relatively high activity as a single agent and in combination with EMP. Further studies are needed to clarify the optimum dose of EMP, taking into account potential cardiovascular toxicity. Phase III studies of its combination with docetaxel are in progress. Copyright 2002, Elsevier Science (USA). All rights reserved. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db =PubMed&list_uids=12121591&dopt=Abstract The role of chemotherapy in advanced prostate cancer. Ernst DS. Department of Medicine, Tom Baker Cancer Centre, Calgary, Alberta, Canada. The development of hormone resistance is an unfortunate final common pathway in most patients with advanced prostate cancer, resulting in a narrowing of therapeutic options for the clinician, and limited median survival of 10-12 months for the patient. While cytotoxic chemotherapy has been utilized for many years, its efficacy has been disappointing. Quality of life assessments are increasingly used in assessing response in hormone-resistant prostate cancer (HRPC), and PSA has emerged as an important surrogate marker of response in both local and advanced disease. Estramustine and the taxanes have been investigated, as monotherapy and in combination, in the treatment of HRPC in phase 2 and 3 clinical trials, a number of which are ongoing. Substantial advances in the management of HRPC over the past decade have led to renewed optimism that improvement in survival can be achieved, and support the belief that chemotherapy plays a role in this pursuit. In tandem with the development of new agents, refined means of assessing response have been developed, and represent a key component of new research strategies in HRPC. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db =PubMed&list_uids=12108899&dopt=Abstract Docetaxel in the integrated management of prostate cancer. Current applications and future promise. Logothetis CJ. Department of Genitourinary Medical Oncology, The University of Texas, M.D. Anderson Cancer Center, Houston 77030, USA. clogothe@mail.mdanderson.org Docetaxel (Taxotere)-based regimens can be included among the most effective treatment options for the management of patients with advanced, androgen-independent prostate cancer. Results with docetaxel as a single agent and in combination regimens with estramustine (Emcyt) have consistently achieved a palliative response, reduced serum PSA levels by > or = 50%, and produced objective responses in patients with measurable disease. In addition, encouraging survival data have been demonstrated in several phase II trials. The ability to administer docetaxel on a weekly basis has substantially enhanced research efforts for treatment in prostate cancer patients. The results of ongoing phase III randomized trials evaluating docetaxel regimens in androgen- independent prostate cancer are eagerly awaited for their potential to definitively demonstrate a beneficial impact on overall patient survival. Docetaxel-containing regimens are likely to demonstrate a substantial role in the management of early-stage prostate cancer patients in the adjuvant and neoadjuvant settings, where clinical investigations are under way. In addition, study results from ongoing trials that integrate docetaxel with hormonal therapies for patients with biochemical recurrence following definitive local treatments will be important in refining the future role of chemotherapy for prostate cancer in general. The preliminary findings from studies conducted with docetaxel are encouraging and await final analysis. Finally, preliminary results from studies exploring combination regimens of docetaxel and novel agents that possess completely different mechanisms of action (eg, proapoptotic agents, angiogenesis inhibitors, and vitamin D analogs) have demonstrated the regimens to be feasible and safe, with promising early response data. These types of investigational studies will likely occupy a dominant position in future research initiatives for patients with advanced prostate cancer. ---------------- From the file chemo.txt Chemotherapy selection criteria Chemotherapy is a treatment option for advanced prostate cancer that has not responded to hormone treatment. Doctors often administer chemotherapy when prostate cancer has spread beyond the prostate. Chemotherapy is sometimes used in combination with other treatments. chemotherapy prostate cancer treatment Effectiveness of chemotherapy The American Cancer Society notes that chemotherapy is not effective against early prostate cancer. It also is not a cure. Chemotherapy may slow tumor growth and reduce pain, but has had limited success in treating advanced prostate cancer. Side effects of chemotherapy Chemotherapy can produce significant side effects. Different chemotherapy drugs cause different side effects. Among the most common side effects are: * Fatigue * Nausea and vomiting * Diarrhea * Mouth sores * Hair Loss * Low white blood cell count * Anemia * Reduced ability of blood to clot bone marrow suppression, liver damage, kidney changes, blood clots, heart attack, or stroke. taxotere http://www.taxotere.com/ Breast and lung cancer? Treatment With Taxotere You and your healthcare team may have decided that Taxotere® (docetaxel) for Injection Concentrate therapy should be part of your breast cancer treatment strategy. There are many more cancer treatment options today than ever before, but when breast cancer progresses after chemotherapy, healthcare professionals often turn to Taxotere. Why Taxotere? In a study of people whose disease progressed after previous chemotherapy, those taking Taxotere showed greater response, longer time before the cancer progressed, and longer survival time than those who took a combination of two other frequently prescribed drugs (mitomycin and vinblastine). Many chemotherapy drugs stop cancer cells from dividing by interfering with the cell's DNA, but Taxotere acts quite differently. Taxotere damages microctubeules—vital structures that are involved in cell division. Taxotere is given intravenously (through a vein) once every 3 weeks. Each treatment takes around 1 hour, and the dosage will vary depending on your medical situation. Taxotere was approved by the Food and Drug Administration (FDA) in 1996 to treat locally advanced breast cancer in patients who have not responded well to chemotherapy with the drug doxorubicin. In 1998, Taxotere was also approved by the FDA to treat breast cancer that has spread into other areas of the breast, or to other parts of the body, after treatment with standard chemotherapy. Like all anticancer agents, there are some side effects associated with Taxotere that you may find difficult to tolerate. These may include low white blood cell count, hair loss, fatigue, fluid retention, numbness, mouth irritation, cutaneous changes, nausea and diarrhea. Many doctors will prescribe additional drugs to help counter these effects. For example, a corticosteroid such as dexamethasone is commonly used to prevent fluid retention while on Taxotere. To learn more about Taxotere, check out Benefits, Side Effects, and Frequently Asked Questions. -------------------- Side Effect Management Chemotherapy medications are powerful so they can work to destroy cancer cells. But because they are so powerful, side effects with chemotherapy are common. Like all anticancer agents, there are some side effects associated with Taxotere® (docetaxel) for Injection Concentrate that may be bothersome or difficult. These may include low white blood cell count, hair loss, fatigue, fluid retention, numbness, mouth irritation, cutaneous changes, nausea and diarrhea. Talk to your doctor if you experience any uncomfortable side effects when you begin Taxotere therapy. Your doctor may prescribe other medications, including a corticosteroid such as dexamethasone, which is used to help avoid or lessen some of the side effects of treatment so you can feel better. Choose a topic to learn more about possible side effects associated with Taxotere: * Low white blood cell count * Fever * Allergic reactions * Fluid retention * Hair loss * Fatigue and muscle discomfort * Rash * Numbness * Nail changes * Nausea, vomiting, and diarrhea * Other Low White Blood Cell Count Your white blood cells protect your body against infection. Taxotere may cause a temporary drop in the number of certain types of white blood cells (a condition known as neutropenia), which may increase the risk of infection. However, most people receiving Taxotere don't have infections, even when their white blood cell counts are low. Your nurse or doctor will routinely draw blood to check your white blood cell count and tell you if your count is too low. Fever Fever is one of the most common and earliest signs of infection. If you have a fever over 100º F, be sure to call your doctor or nurse immediately. Other symptoms of infection, such as sore throat, cough, or a burning sensation while urinating should also be reported. Allergic Reactions This type of reaction, which may occur during the infusion of Taxotere, is infrequent. If you feel a warm sensation, a tightness in your chest, difficulty in breathing, or itching during or shortly after treatment, tell your doctor or nurse immediately. A corticosteroid such as dexamethasone is taken before you receive Taxotere to reduce the severity of these reactions. It is important that you take your corticosteroid exactly as your doctor or nurse advises you. Fluid Retention Fluid retention is a term used to describe an accumulation of fluid in body tissues and/or body cavities. Normally your body will eliminate any extra fluid. Taxotere may interfere with this process, and extra fluid may appear as swelling of your feet or hands, or as a weight gain of up to several pounds. It is important for you to let your doctor or nurse know if you have any signs of fluid retention. Watch for swelling of your feet or hands. Weigh yourself regularly so you will know if you have gained weight. A corticosteroid such as dexamethasone is taken before you receive Taxotere to reduce the severity of these reactions. It is important that you take your corticosteroid exactly as your doctor or nurse advises you. Hair Loss Loss of hair (including the hair on your head, underarm hair, pubic hair, eyebrows, and eyelashes), which is known as alopecia, occurs in most people taking Taxotere although some may experience only thinning in these areas. For some people, this is a very difficult side effect to experience. However, your hair should grow back once you stop treatment. Meanwhile, your doctor or nurse can refer you to a specialty store that carries wigs, hairpieces, and turbans specifically for patients with cancer. You can also call the American Cancer Society for more information (1-800-ACS- 2345). Talking to other cancer survivors in a support group may help you greatly at this time. Fatigue and Muscle Discomfort Many patients receiving Taxotere feel tired at some time during their treatment. Even if you are only slightly tired, make sure you get enough rest during your treatment. If you feel prolonged fatigue during the course of your treatment, tell your doctor or nurse. There are medications that can help reduce your fatigue. Muscle discomfort due to Taxotere is rarely severe. If you feel pain or aching in your muscles or joints, tell your doctor or nurse. He or she can suggest ways to make you more comfortable. Rash People receiving Taxotere may develop a red, blotchy rash. This usually occurs on the feet and hands, but may also appear on the arms, face, or body. If it occurs, the rash generally appears within the week after Taxotere treatment and usually disappears after a week or two. While this rash is rarely severe, be sure to tell your doctor or nurse if it occurs. Numbness Some patients receiving Taxotere experience numbness, tingling, or burning sensations in their fingers and/or toes. This side effect usually occurs after several cycles of Taxotere and goes away after treatment has ended. Nail Changes Changes in the color of your nails may occur while you are taking Taxotere. Occasionally, nails become soft and tender. In rare cases, nails may fall off. After you have finished Taxotere treatment, your nails will generally grow back. Keeping your nails clean and trimmed and using a nail hardener while being treated with Taxotere may help prevent nail problems. Nausea, Vomiting, and Diarrhea Nausea, vomiting, and diarrhea may occur, but generally are not severe with Taxotere. Let your doctor or nurse know if you experience these side effects. There are medications available to make you feel more comfortable. Other Possible Side Effects The side effects listed here include those that occur most frequently in breast cancer patients receiving Taxotere, but they are not the only ones that may occur. Be sure to report any symptoms to your doctor or nurse. -------------- Interaction With Other Drugs It is very important that you only take medications that your doctor prescribes for you. During treatment for cancer, you may take many different types of medications, both to treat cancer and to ease bothersome side effects. Since it can be confusing to remember all the names of the medications, it's important that you keep a written record of all of your current prescription and non-prescription (over-the-counter) medications. Certain medications can react with each other (even simple over-the-counter drugs) and cause unwanted side effects, or even become ineffective. Be sure that the doctor who is giving you Taxotere® (docetaxel) for Injection Concentrate knows about all other medications you are taking. Tell your doctor about non-prescription drugs that you use and medications prescribed by other doctors. Likewise, make sure any other doctors who treat you know that you are receiving chemotherapy. 1-800-633-1610 U.S. Headquarters: Aventis Pharmaceuticals 300-400 Somerset Corporate Boulevard Bridgewater, NJ 08807-2854 Phone: 1-800-981-2491 ------------------------- Docetaxel is chemotherapy that is given as a treatment for some types of cancer. This factsheet describes docetaxel, how it is given and some of its possible side effects. It should ideally be read with CancerBACUP's booklet Understanding chemotherapy, which gives more information and advice. Each person's reaction to chemotherapy is unique. Some people have very few side effects, while others may experience more. The side effects described in this factsheet will not affect everyone who is given docetaxel, and may be different if you are having more than one chemotherapy drug. We have outlined the commonest and less common side effects, so you can be aware of them if they occur. However, we have not included those which are very rare and therefore extremely unlikely to affect you. If you do notice any effects which you think may be due to the drug, but which are not listed on the factsheet, please discuss these with your doctor or chemotherapy nurse. You will see your doctor regularly while you have this treatment so that they can monitor the effects of the chemotherapy. This factsheet should help you to discuss any queries about your treatment and its side effects with your doctor or chemotherapy nurse, as they are in the best position to help and advise you. What it looks like A yellow/brown liquid which, when diluted, forms a clear solution. How it is given As an infusion (drip) into a vein (intravenously) through a fine needle (cannula) inserted into the vein. Possible side effects Temporary reduction in bone marrow function. This can result in anaemia, risk of bruising or bleeding and infection. This effect can begin about 7 days after the treatment has been given and usually reaches its lowest point at 10-14 days after the chemotherapy. Your blood count will then increase steadily and will usually return to normal within 21 days. The extent to which your blood count is reduced depends on the dose of chemotherapy you receive and which other chemotherapy drugs, if any, are given in combination. Your doctor can advise you how likely it is that your blood count will be lowered by the chemotherapy. Your blood count will be checked regularly to see how well your bone marrow is working. If your temperature goes above 38C (100.5F), or you develop any unexplained bruising or bleeding, or you suddenly feel unwell, even with a normal temperature, contact your doctor or the hospital straight away. Nausea and vomiting. This is usually mild. There are now very effective anti-sickness drugs to prevent or substantially reduce this. If it does happen it may begin a few hours after the treatment is given. If the sickness is not controlled, or continues, tell your doctor. They can prescribe other anti-sickness drugs which may be more effective. Mouth sores and ulcers. If your mouth becomes sore, or you notice small ulcers, let your doctor know. They can prescribe suitable mouth care for you. Diarrhoea. This can usually be easily controlled with medicine but let your doctor know if it is severe or persistent. It is important to drink plenty of fluids if you do get diarrhoea. Hair loss. This usually starts 2-3 weeks after the first dose of docetaxel, although it may occur earlier. Hair may be lost completely or may just thin. You may also experience thinning and loss of eyelashes, eyebrows and other body hair. This is temporary: the hair will return to normal once the treatment is finished. CancerBACUP has a booklet called Coping with hair loss which we would be pleased to send you. Skin changes. Docetaxel can cause a rash. Your doctor can prescribe medicine to help with this. Soreness and redness of the palms of the hands and soles of the feet (sometimes known as Palmar Planter syndrome). This is temporary and will improve when treatment is finished. Allergic reaction. Signs of an allergic reaction include skin rashes and itching, high temperature, shivering, redness of the face, a feeling of dizziness, headache, shortness of breath, anxiety and a need to pass urine. You will be monitored for any signs of an allergic reaction during the treatment. Tell your doctor or nurse if you have any of these symptoms. A course of steroids is often prescribed to reduce the chance of developing an allergic reaction and to help reduce other side effects. Tiredness and a general feeling of weakness. It is important to allow yourself plenty of time to rest. Fluid retention. You may notice that you gain weight and/or that your ankles and legs swell. This decreases slowly once your treatment has finished. Sometimes drugs can be given before you receive docetaxel to limit the fluid retention. Less common side effects Numbness or tingling in hands or feet. This is due to the effect of docetaxel on nerves. You may also notice that you have difficulty doing up buttons or other fiddly tasks. Tell your doctor if you notice any numbness or tingling in your hands or feet. This usually improves slowly a few months after the treatment is finished. Changes in nails. The colour of your nails may change. This change grows out over several months once the treatment has finished. Pain in the nail bed may occur, but this is rare. Pain in the joints or muscles. It is important to tell your doctor about this so that appropriate painkillers can be prescribed. Additional information While docetaxel is being given, it can cause pain where the injection is made, or along the vein. If you feel pain, tell the doctor or nurse. If you notice any stinging or burning around the vein while the drug is being given, or any leakage of fluid from the cannula site, it is very important that you tell the doctor or nurse immediately. If the area around the injection site becomes red or swollen at any time let the doctor or nurse know. Fertility. Your ability to conceive or father a child may be affected by taking this drug. It is important to discuss fertility with your doctor before starting treatment. Contraception. It is not advisable to become pregnant or father a child while taking docetaxel as it may harm the developing foetus. Again, discuss this with your doctor. References British National Formulary (BNF) A joint publication of the British Medical Association and the Royal Pharmaceutical Society of Great Britain. For more information call CancerBACUP's Cancer Support Service on 020 7613 2121 or Freephone 0808 800 1234 to speak to a cancer specialist nurse. Lines are open Monday-Friday, 9am-7pm. This information has been compiled by CancerBACUP's Support Service. We thank the patients and specialist advisers who have helped in the production of this factsheet. Last reviewed/updated: December 2001 ------------------------- http://www.tirgan.com/taxotere.htm htirgan@tirgan.com This drug is prepared from the needles of European yew trees. It is from the same family of Taxol. It has shown significant activity in following cancers: * Breast cancer. This drug was approved by FDA in May 1996 for treatment of patients with advance stage breast cancer who have failed to respond to Adriamycin. * Non small cell lung cancer