Gemcitabine [Gemzar] compiled by doctordee | Search LMS site |

General Considerations URLs for Patient Information Descriptive Information Clinical Trial Results
General Considerations
A chemotherapy cocktail regimen of Gemcitabine + taxotere [docetaxel] can give a 50 to 60% response in Uterine LMS [1], and be active in sarcomas generally. Yet can trigger a serious pulmonary condition and a fatal cardiac condition. [2] Potent drugs are potent drugs. The most effective schedule for infusion is yet to be proved. Lesser amounts of gemcitabine might be more effective [and are more toxic] if infused at the rate determining step over a longer period of time. Currently, the infusion rate for gemcitabine use in LMS is set at 90 minutes. Gemcitabine has been shown to be a potent radiosensitizer, and this property has been used to downsize LMS tumors in chemoradiation regimens. However, gemcitabine lung reactions occur more frequently in patients who have had prior radiation to the mediastinum.[2] [1] A recent clinical trial of the combination of gemcitabine and docetaxel reported favorable results in patients with unresectable, predominantly uterine leiomyosarcoma (LMS). The objective of this report is to describe additional experience with this combination in a variety of histologic subtypes of sarcoma. Responses occurred in 6/10 LMS from various primary sites, and in total there were 5 complete responses and 8 partial responses for an overall response rate of 54%. 2002 CTOS Annual Meeting Posters Medical Oncology Abstract ID: 80 GEMCITABINE AND DOCETAXEL IN SARCOMA Kirsten M. Leu1, Mark Zalupski1, Vernon Sondak1, Krisinda Snyder1, Laurence H. Baker1 University of Michigan Comprehensive Cancer Center, MI, United States kmleu@umich.edu [2]Gemcitabine cardiac and pulmonary toxicity ran 10% in this study and prior mediastinal radiation increased the pulmonary complications to 2 out of three. Severe Nonhematologic Toxicity After Treatment with Gemcitabine ASCO 2313 - 1999 "We report a series of 4 out 56 patients (7.1%) treated with gemcitabine who developed an unexplained noncardiopulmonary distress syndrome most likely related to gemcitabine. One further patient developed ventricular arrhythmia immediately after gemcitabine exposure leading to cardiac arrest." " In 5 patients... we assumed that gemcitabine is related to pulmonary or cardiac toxicity, respectively. In 3 patients reexposure resulted in identical toxicity. One patient did not receive further gemcitabine treatment due to life threatening primary event. In one patient pleural effusion occurred. Two patients had prior [recent] radiation to the mediastinum" " Life threatening pulmonary toxicity after gemcitabine treatment was more common than initially anticipated. Gemcitabine should be used with caution in patients who received prior radiation to the mediastinum"
URLs for Patient Information
Gemcitabine - Gemzar Online Information for Patients Manufacturer's Package Insert The manufacturer's package insert should be consulted for detailed information on the usual cautions, precautions, and contraindications of the use of this drug.. This Eli-Lilly PDF File on Gemzar requires the Acrobat Reader program on your computer. It can be downloaded for free. CancerBacup Drug Information MedlinePlus Drug Information CancerSource Drug Information Medscape Drug Information. Registration is free. Gemzar Website Search Pubmed for ALL articles on Gemcitabine
Descriptive Information
Preparation: GEMCITABINE HCL INTRAVENOUS Available for injection or IV infusion, as 200mg of gemcitabine hydrochloride, or 1 gram of gemcitabine hydrochloride. It is a white powder which reconstitutes to a clear liquid. Manufactured by Lilly. Store the unopened vials away from light and moisture at room temperature [20 to 25 degrees C., or 68 to 77 deg F.]. The reconstituted solution is stable for 24 hours at room temperature, and should be inspected for particulate matter or discoloration. If either is present, do not use the liquid. Do not refrigerate the solution, as the drug may precipitate. Discard any unused liquid. Gemcitabine hydrochloride is a synthetic pyrimidine nucleoside, and is an antineoplastic agent. Diseases for which it has been approved are pancreatic cancer, bladder cancer, non-small cell lung cancer and soft tissue sarcoma. This medication may be used alone or in addition to other cancer treatments. Mechanism of Action [also see Chemistry and Pharmacology below] Once inside the cell, it requires activation by an enzyme [deoxycytidine kinase] to a cytotoxic metabolite of a triphosphate nucleotide [dFdCTP]. Gemcitabine's tumoricidal activity depends upon the balance between activation, degradation, and the formation of the cytotoxic triphosphate compounds. It has several mechanisms of action, most of them interfering with DNA synthesis or the enzymes responsible for DNA synthesis, during the Synthesis phase of the cell cycle. Gemcitabine is a look-alike for a DNA component, but when gemcitabine is used in the DNA strand, it sabotages further synthesis. It also reacts with DNA polymerase enzymes to prevent DNA synthesis and repair. It also inhibits other enzymes, and creates problems for RNA synthesis as well. Metabolism There is poor oral absorption because of degradation within the gastrointestinal tract. If Gemcitabine is administered intravenously, SLOWLY, over a period of time greater than 70 minutes, the drug will distribute slowly and widely throughout the tissues. Shorter infusion times prevent extensive distribution of the drug. This medication is usually given by vein over 30 minutes. Gemcitabine does not cross the blood-brain barrier, so it cannot be used for brain metastases. Gemcitabine undergoes degradation by deamination by cytidine deaminase present in liver, plasma and peripheral tissues. The elimination half-life depends upon the infusion time. For short infusions, the half-life is 30 to 90 minutes, for infusions over seventy minutes, the half-life is 4 to 10 HOURS, and is associated with increased toxicity. Clearance depends upon gender and age: it is 30% less in women and the elderly. Dosage Range: For more information about this, see section below on Dosage and Management. For pancreatic cancer, 1000 mg/m2 IV every week for 7 weeks with one week rest. Treatment then continues weekly for 3 weeks followed by one week off. For bladder cancer, 1000 mg/m2 IV on days 1, 8, 15 every 28 days. For non-small cell lung cancer, 1200 mg/m2 IV on days 1, 8, 15 every 28 days. The dose depends on the patient's condition and response to therapy. Do not exceed the maximum recommended dose. BEFORE taking Gemcitabine: Before taking this drug, notify your doctor of any of the following: If you have chickenpox or exposure to chickenpox, gout, heart disease, congestive heart failure, shingles, kidney stones, liver disease, recent/upcoming vaccinations (e.g., oral polio, measles, flu). Tell your doctor of any recent illness, radiation therapy, kidney problems, liver problems, bone marrow problems ( leukopenia, thrombocytopenia, anemia), allergies (especially drug allergies). Do not start or stop any medicine without your doctor's approval. Tell your doctor if you are taking any other prescription or over-the-counter drugs, including vitamins and herbals. Ask whether Gemzar will have a reaction or effect with your usual foods, alcohol, activities, prescription and nonprescription medications. Foods or alcohol can react with drug products. Don't take a new medication, prescription or over-the-counter, without asking your doctor or nurse if it will react with your other medications, or alcohol or foods. Always ask for and read the package inserts on any medication you are taking. Drowsiness or dizziness can be a side effect for this drug, and it can affect driving, using machinery, or cooking with hot oil. Report to your doctor any use of drugs that can cause additional drowsiness: sleeping pills, sedatives, tranquilizers, anti-anxiety drug (e.g., diazepam), narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., phenothiazines or tricyclics), anti-seizure drugs (e.g., carbamazepine), muscle relaxants, drowsiness-causing antihistamines (e.g., diphenhydramine). Check labels or package inserts on all medicines (even over the counter products) because they may contain substances that cause drowsiness. Limit alcohol usage as it may aggravate fatigue or drowsiness. Do not take this drug if you are, or become, pregnant. If you are pregnant, breast feeding or planning children in the future, inform your doctor of this before taking Gemzar. Gemzar can cause birth defects if either parent is taking it at the time of conception, or if the mother is taking it during pregnancy. Men and women who are taking Gemzar must use effective birth control. However, do not use oral contraceptives without checking with your doctor. Because many chemo drugs cause sterility, discuss any planning for future children with your doctor. In the presence of the following conditions, there may be additional risk if gemcitabine is taken: BONE MARROW SUPPRESSION HEPATIC FUNCTION IMPAIRMENT INFECTION RENAL FUNCTION IMPAIRMENT Conditions of Use: 1. Blood counts must be monitored regularly. Toxicity to bone marrow is a dose limiting condition, and dose will be reduced if need be. 2 In patients with abnormal liver or renal function, there is increased risk of toxicity. Dose may be reduced in these cases. 3. Infusion time greater than 60 minutes is associated with increased toxicity. 4. Women and the elderly have decreased gemcitabine clearance. Caution is advised because of possible increased toxicity. 5. If there is difficulty in urination, or change in color of the urine, especially if it turns red or brown, the doctor must be notified. 6. Not for use in pregnancy. 7. Keep all scheduled medical appointments. 8. MISSED DOSE: If you miss a dose, contact your doctor immediately to establish a new dosing schedule. Drug Interactions With Cisplatin: Gemcitabine increases reactions between cisplatin and DNA, and therefore increases Cisplatin's cytotoxicity. With Etoposide: Etoposide increases Gemcitabine's cytotoxicity. With Radiation: Gemcitabine is a strong radiosensitizer. Radiation recall reactions can also occur. Gemcitabine is used in combination with many other agents, in clinical trials, at present. Side Effects Everybody's reaction to chemotherapy is different. You may have very few side effects, while others may have more. Tell your doctor all the symptoms you experience. There is often medication to treat or prevent side effects. Bone Marrow: Suppression of Bone Marrow [myelosuppression] is dose limiting. Low white cell counts [leukopenia] are more common that low platelet counts [thrombocytopenia]. Lowest counts occur by day 10-14, and generally recover by day 21. Low red blood cell counts [anemia] can also occur. Gemcitabine can lower your ability to fight off an infection. Low white cell counts mean that infections can become very serious, report sore throats, or fevers over 100.5 deg, or chills or if you suddenly feel unwell, even with a normal temperature, to your doctor promptly. Low platelet counts favor extra or excessive bleeding or bruising, likewise tell your doctor. Gastrointestinal: Nausea/vomiting, mild to moderate, 70% of patients. They may begin a few hours after the treatment and last up to a day. There are very effective drugs that your doctor can give to prevent nausea and vomiting. If the nausea and vomiting is not controlled, or continues, tell your doctors. They can prescribe other anti-emetics that will be more effective. Loss of appetite. This is also usually mild and may last a day or so. It is important to eat properly during chemotherapy treatments. Mouth sores and ulcers. If your mouth becomes sore, or you notice small ulcers, ask your doctor to prescribe suitable mouth care for you. Diarrhea is common. It is easily controlled with medicines, but it is important to drink plenty of fluids, including some potassium rich fluids and foods as well [orange juice, tomato juice, bananas]. Tell your doctor if the diarrhea is severe or persistent. Constipation. Flu-like illness: fever/ malaise/ chills/ headache/ muscle aches, 20% of patients. Occasionally a flu-like illness may occur with headaches, and aching joints and muscles and fevers. You should always let your doctor know about a fever. Fever: without infection, within 1st 12 hours, mild, 40% of patients. Liver: changes in liver function, with raised enzymes [serum transaminases and bilirubin]. This is a temporary effect, and liver function returns to normal when the treatment is finished. Lungs: Inflammation/difficulty breathing/cough pulmonary toxicity. Infusion reaction: flushing/ facial swelling/ headache/difficulty breathing and/or low blood pressure/faintness. Will probably resolve with slowing or stopping infusion, seems to be related to the rate of infusion. Urinary: Small amounts of protein and blood in the urine. Hemolytic uremic syndrome [HSU] has occurred. Notify the doctor if the urine turns red or brown. Skin: Skin rash/itching. pain/redness at the injection site. Hair usually thins but is not lost completely, and this is a temporary effect. Hair will re-grow after treatment is finished. Ankle Swelling: You may also notice some mild swelling of your ankles, which will go away after the treatment finishes. 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. Other, serious side effects: Tell your doctor of them immediately. Loss of appetite. Tingling or numbness of the hands and/or feet. Trouble sleeping. Unusual sweating. Hearing changes. VERY SERIOUS side effects. Tell your doctor immediately. Pain at injection site. Severe headache. Irregular or very fast pulse. One-sided weakness. Mental or mood changes. ANY Vision problems. Slurred speech. Chest pain. Difficulty breathing. Urine amount changed or urine color dark. Eyes or skin turn yellow [jaundice]. High blood pressure. Marked Edema or swelling. Intractable Drowsiness. Pins & needles feelings or numb feelings in any part of your body. Allergic reactions to Gemcitabine are unlikely, but require immediate medical attention. Symptoms would include rash/ itching/swelling, dizziness, trouble breathing. For other effects not listed here, contact your doctor. OVERDOSE: For a suspected overdose, contact your emergency room or local poison control center or immediately. Symptoms of overdose may include severe tiredness, rash, or tingling or numbness of the hands or feet. Your condition can cause complications in a medical emergency. For information on enrollment call Medic Alert (TM) at 1-800-854- 1166. In Canada call 1-800-668-1507. Chemistry and Pharmacology This gets a bit complicated, but explains why the infusion rate makes a difference in Gemcitabine activity and toxicity. Gemcitabine is a lookalike for one of the molecules that is used to make DNA. This is called being a "nucleoside analog'. When it is taken by the enzymes and put into the DNA molecule, further synthesis [building up] of that DNA molecule stops, because the gemcitabine is the wrong shape and size to allow further synthesis. Gemcitabine consists of the pyrimidine base difluorocytidine, and the sugar part called deoxyribose. This mimics one of the nucleosides that is used to make DNA. It is called an antimetabolite antineoplastic agent. Gemcitabine works in a specific part of the cell cycle, at the beginning of [the G1-S border] and during [the S phase] the DNA synthesis phase of the cell cycle. It causes arrest of the progression into mitosis, because the DNA is not being made. In order to be effective, the gemcitabine is converted within the cell to 5-diphosphate and -triphosphate products. The names of the first one are deoxydifluorocytidine-5-phosphate [de oxy di fluoro cytidine 5 phosphate] or dFdCDP or gemcitabinediphosphate. The names of the second one are deoxydifluorocytidine-triphosphate, or dFdCTP or gemcitabinetriphosphate. Unchanged gemcitabine is not active. It has its first phosphate group added, to form gemcitabine monophosphate, but an enzyme called deoxycytidine kinase [deoxy cytidine kinase]. The gemcitabine monophosphate then has another phosphate added to the molecule by another enzyme called deoxycytidylate kinase [deoxy cytidylate kinase]. The gemcitabine diphosphate can then have another phosphate added to it by yet another enzyme, nucleoside diphosphate kinase, and becomes gemcitabine triphosphate. The two active products of gemcitabine have combined actions that lead to prevention of DNA synthesis. Gemcitabine diphosphate inhibits an enzyme called ribonucleotide reductase, which catalyses the formation of deoxynucleoside triphosphates needed for creating DNA molecules. Gemcitabine diphosphate probably reacts with this enzyme, but because it is not really the right molecule, it doesn't let go. So the reductase enzymes are stuck with this big, indigestible hulking fake nucleoside, which is stuck to its active site, and which won't let go. By preventing this reductase from working, gemcitabine diphosphate interferes with production of the other nucleosides that go to make up the DNA. Gemcitabine triphosphate inhibits DNA synthesis by 'looking' like deoxycytidine triphosphate, the REAL nucleoside, and reacting with DNA polymerase. [The DNA polymerase is an enzyme that picks up nucleosides and sticks them onto the DNA chain that is being built.] So when the DNA polymerase scoops up the gemcitabine triphosphate, and sticks it into the DNA chain, it is just doing its job. BUT once the gemcitabine triphosphate is put into the DNA chain, the DNA chain will take just one more nucleotide, and then stops growing. The DNA polymerase enzyme is unable to recognize the abnormal (gemcitabine triphosphate) nucleotide and remove it, because it is hidden behind the terminal normal nucleotide. This process is called "masked chain termination". With the stopping of DNA growth, and the gross DNA damage which cannot be repaired, the cell undergoes apoptosis [it commits suicide. Unless the intracellular mechanisms that initiate and encourage apoptosis are impaired.] This inability of the cell to recognize and remove the abnormal gemcitabine nucleotide results in a longer intracellular half-life of gemcitabine compared with the other fake nucleosides such as cytarabine. The "masked chain termination" that flummoxes intracellular DNA repair is thought to be one of the reasons that gemcitabine is more active than the other fake nucleosides. Now, remember that gemcitabine Diphosphate prevents the formation of other nucleotides? Including deoxycytidine triphosphate, which is the REAL nucleotide that the TRIphosphate replaces? This means that the gemcitabine triphosphate is more likely to be incorporated into cell DNA, because the real enzyme substrate is prevented from being manufactured by gemcitabine diphosphate. So the one metabolite of gemcitabine decreases the agent that the OTHER metabolite is competing with... a nice piece of teamwork between the two metabolites. This process is called "self-potentiation". Resistance occurs by decreased transport into cells, decreased activation of the drug through decreased expression of the activating enzyme, increased degradation, or increased concentration of the nucleotide it competes with, through increased expression of the enzyme that synthesizes it. Dosage and Management: Dosage of gemcitabine hydrochloride is individualized based on the cancer treated, body surface area and patient tolerance and response. Safety of Gemcitabine use in children younger than 18 years of age has not been established. Gemcitabine should not be administered more frequently than once a week, because the toxicity is increased unacceptably. During a phase I trial assessing maximum tolerated dosage with a schedule of 5 consecutive daily doses, intolerable hypotension and flu-like symptoms developed at gemcitabine doses higher than 10 mg/m2daily. The occurrence and degree of those side effects were dose related. In other phase I trials using twice a week dosing schedules, the maximum tolerated gemcitabine doses were 65 mg/m2 when the drug was infused over 30 minutes and 150 mg/m2 when the drug was injected over 5 minutes. In these trials, the limiting toxicities included thrombocytopenia, flu-like symptoms, and loss of strength and energy. Dosage Escalation. Dosage escalation can be considered for patients who complete the initial 7-week or subsequent 3-week cycle of gemcitabine at the full weekly dosage of 1 g/m2, provided that the lowest of the absolute granulocyte and platelet counts exceed 1500 and 100,000 per mm3 respectively, and nonhematologic toxicity does not exceed a World Health Organization (WHO) grade of 1. For these patients, the dosage can then be increased to 1.25 g/m2 weekly. If this dose is given for a complete 3-week course and the above hematological and WHO parameters are still met, then dosage can be increased to 1.5 g/m2 weekly given in 3-week cycles. Dose Adjustment for Hematologic Toxicity A complete blood cell count with differential and platelets should be done before each dose of gemcitabine. If hematological toxicity is detected, the gemcitabine dose should be decreased or temporarily withheld according to the degree of myelosuppression. For absolute granulocyte counts of at least 1000/mm3 and platelet counts of at least 100,000/mm3, no dose adjustment. For absolute granulocyte counts of 500 to 999/mm3 or platelet counts of 50,000 to 99,000/mm3, 75% of the full dose should be given weekly. If the absolute granulocyte count is less than 500/mm3 or the platelet count is less than 50,000/mm3, withhold the weekly dose until the counts exceed these levels. Dosage Adjustment in Renal and Hepatic Impairment The effect of renal or hepatic impairment on gemcitabine's disposition is not known, since it has not been studied systematically in patients with substantial renal or hepatic dysfunction. So, while there are no specific recommendations for use, gemcitabine should be used with caution in such patients. Some Regimens for Examples of How it is Used: Gemcitabine monotherapy: Gemcitabine dosages of 1000 or 1250 mg/m2 administered by 30-minute IV infusion once weekly for 3 weeks followed by 1 week of rest have been used commonly. Gemcitabine dosages of 1000 mg/m2 administered once weekly for 3 weeks on a 4-week cycle or 1250 mg/m2 administered once weekly for 2 weeks on a 3-week cycle have also been used in large randomized trials. Another regimen, for the initial cycle, Gemcitabine is 1 g/m2 once weekly may be repeated weekly if tolerated for up to 7 weeks, followed by a week of rest. During the initial cycle, the dose must be reduced or withheld if there is a significant degree of bone marrow toxicity. Subsequent cycles' dosage is weekly administration for 3 consecutive weeks of the usual dose [or escalated dosage, if tolerated, or reduced dosages according to the amount of bone marrow toxicity] followed by a week of rest. In the clinical trials, women tolerated the drug more poorly than men, were less likely to continue subsequent cycles, and were more likely to experience neutropenia and thrombocytopenia. Because Gemcitabine clearance is reduced in women and geriatric patients, dosage reductions [as recommended in general for bone marrow toxicity] are more likely in these populations. Infusion time: The conversion of gemcitabine to its active triphosphate is the rate limiting step in its potency. If one gives the gemcitabine at a slow rate, that maintains high levels of the triphosphate, without wasting excess gemcitabine, presumably the effectiveness of the gemcitabine will be enhanced. Investigations into this alternative are promising, and are evidently tolerated well. The use of a portable infusion pump allows for lengthy infusions as an outpatient, or at home. gemcitabine in combination: When using two or more chemotherapy agents in combination, toxicities are often greater to MUCH greater than agents used singly. Reducing or withholding doses of both agents is more common. Which problems predominate depends upon the agents being used, but hematological toxicity is very common. in combination with cisplatin: Gemcitabine doses of 1000 to 1500 mg/m2 have been used in combination with cisplatin in phase II studies. For initial treatment of inoperable stage III or IV non-small cell lung carcinoma, the combination of gemcitabine and cisplatin may be administered on either a 3 or 4 week specific dosing schedule. The 4 week schedule: Gemcitabine 1000 mg/m2 administered by 30-minute IV infusion on days 1, 8, and 15 of each 28-day cycle. Cisplatin IV 100 mg/m2 administered on day 1 following completion of the gemcitabine infusion. The 3 week schedule: Gemcitabine 1250 mg/m2 administered by 30-minute IV infusion on days 1 and 8 of each 21-day cycle. Cisplatin IV 100 mg/m2 should be administered on day 1 following completion of the gemcitabine infusion. Dosage of gemcitabine should be reduced or withheld according to the degree of hematologic toxicity. For adjustment of cisplatin dosage according to the degree of hematologic toxicity, see the manufacturer's prescribing information. Gemcitabine and cisplatin doses should be withheld or reduced by 50% for severe (grade 3 or 4) nonhematologic toxicity other than alopecia or nausea and vomiting. Careful monitoring of serum creatinine, potassium, calcium, and magnesium is recommended in patients receiving gemcitabine + cisplatin. Appropriate administration, hydration, and dose adjustment guidelines for cisplatin should be followed.
Clinical Trial Results
The Clinical Trials results are the experiments done in the past to see if the drug works, and how well, and for how long. There is a list of all clinical trials using Gemcitabine on the NCI PDQ Database. Current Clinical Trials with Gemcitabine From the PDQ Trials Search Page Go to the "Type Of Cancer" search window, and select either Soft Tissue Sarcoma [adult] or Uterine Sarcoma Find the Drug selection window Browse the drug list, and select the drug [so you don't have spelling problems]. Go to the bottom of the page, and click on "search now" The Search Result page will appear. If you click on the title of the Study, more information about the study will appear. PubMed Searches Directions for use: When you click on the search string, it will connect you to Pubmed and display the first 20 citations [which they will call Summaries]. What you WANT is the complete listing of all the summaries of the article [which they will call Abstracts. ] Go to the second toolbar, and use the drop down menu to change summaries to Abstracts, and 20 to 200, and sort by DATE, and then click on DISPLAY on that same toolbar. You may have to wait while the page loads. NOW you can save this search to a folder on your hard drive as "GemzarClinicalTrials" as an HTML file - or as a text file. The entire file, or just those parts which you wish to discuss, can be printed out and taken to talk over with your doctor. Search Pubmed for gemcitabine clinical trials and LMS Search Pubmed for gemcitabine clinical trials and sarcoma Search Pubmed for LMS clinical trials and gemcitabine + taxotere Search Pubmed for sarcoma clinical trials and gemcitabine + taxotere ASCO Searches You will have to go to the site and search year by year with keywords of the chemotherapy agent AND sarcoma. ASCO Search Page The results of a partial search are listed below. ASCO medical abstracts are all under copyright. Use the links to view the complete & detailed abstracts. You may make one copy of any copyrighted article for your personal use. A Phase II Trial of Gemcitabine, Paclitaxel and Carboplatin in Stage IVB Soft Tissue Sarcoma. Responses of 5 sarcoma patients in a phase I study prompted further investigation. ... A complete response in one angiosarcoma [for 6 months], there was one partial response, and 7 stable disease [9/22 = 41%]. The regimen is not without hemotological or hepatic toxicity. ASCO 2930 - 2001 Docetaxel (D) Plus Gemcitabine (G) is Active in Leiomyosarcoma (LMS): Results of a Phase II Trial. 16 evaluable patients: 3 CR, 5 PR [50% decrease in lesion size]= 50% Response Rate. Most were ULMS, and many had been unresponsive to doxo and ifos. Toxicity: bone marrow, dyspnea, fatigue, neurotoxity ASCO 1408 - 2001 Phase I Study of Low Dose Continuous Infusion Gemcitabine in Sarcoma Patients. The conversion of gemcitabine to its triphosphate is rate limiting, and proceeds equivalently to 10mg/m2/min IV. 9 Phase I patients with refractory STS were given gemcitabine as a 72 hour infusion, every 2 weeks. Dose escalation was 50, 75, 100, 150 mg/m2, increasing every 2 cycles [in the absence of toxicity]. ASCO 2935 - 2001 Phase I Pharmacokinetic Trial of the Farnesyl Transferase Inhibitor SCH66336 Plus Gemcitabine in Advanced Cancers. "Farnesyl transferase inhibitors (FTI) are a new class of drugs that inhibit post-translational C-terminal modification of many essential proteins including ras, rac, rho and most cellular g-proteins. SCH 66336 is a potent, orally bioavailable FTI that possesses in vivo and in vitro activity against a wide variety of human tumor... cell lines and xenografts." "SCH66336 and gemcitabine has led to an impressive disease stability in a variety of refractory solid tumors" ASCO 717 - 2000 Phase I Study of the Combination of Taxotere, Gemcitabine and CPT 11 in Patients with Refractory Malignancies. ASCO 832 - 2000 A Phase I Trial of Gemcitabine (GEM) and Paclitaxel (PAC) in Patients with Advanced Solid Tumors, Administered Every 21 Days (LOA-2). One patient with a soft tissue sarcoma achieved partial response. ASCO 848 - 2000 Phase I Trial of Three-Hour Infusion Gemcitabine (GEM) (Days 1,8,15 Every 28) in Refractory, Heavily Pretreated (HP) Advanced Solid Tumors. ASCO 855 - 2000 Biweekly Docetaxel (DOC), Gemcitabine (GEM) and Oxaliplatin (LOHP) in Pretreated Patients with Solid Tumors. Results of a Phase I Study. 31 patients, 5 sarcoma. 22pts evaluable for efficacy: PR5 [23%] SD 13 [59%]; progressive disease 4 [18%]. ASCO 862 - 2000 RFS 2000 (9-NC) with Short or Constant Rate Infusion Gemcitabine (GEM) in Patients (Pts) with Refractory Tumors. ASCO 863 - 2000 Phase I Study of Gemcitabine and Docetaxel for Locally Advanced and/or Metastatic Cancer of the Head and Neck, Non-Colorectal Gastrointestinal Cancer, Hepatoma, and Soft Tissue Sarcoma. "The maximum-tolerated-dose of docetaxel with gemcitabine is 70mg/m2 and a phase II study in selected primary sites is planned." ASCO 866 - 2000 Limited Activity and Acceptable Toxicity of Gemcitabine in a Phase II Study of Patients (Pts) with Advanced Sarcomas: A Mayo Cancer Center Study. We evaluated gemcitabine in pts having histologically confirmed sarcomas. 26 of 30 pts are evaluable. There were 9 leiomyosarcoma (5-GI, 3-intrabdominal, 2-IVC, 2-extremity, and 2-uterine) "1% of pts have progressed and 23% have died. 77% of pts discontinued treatment due to progression and 12% due to toxicity/refusal. One partial response was observed in a uterine leiomyosarcoma pt lasting at least 3 months. Overall response rate is 3%." "This regimen is not recommended for advanced sarcomas." ASCO 2188 - 2000 Biweekly Docetaxel (Doc), Gemcitabine (Gem), Oxaliplatin (LOHP) in Heavily Pretreated Patients with Solid Tumors-A Pilot Study. 10 pts with refractory tumors, 8 evaluable for response, 2/8 objective remissions [the only sarcoma], 4/8 other clinical response ASCO 789 - 1999 Gemcitabine, Carboplatin, and Paclitaxel: An Active, Tolerable Treatment for Advanced Malignancy. "Of the 14 patients evaluable for response, only two patients demonstrated progressive disease after two cycles. 6/14 patients had objective evidence of response, including one CR (bladder), two PRs (1 pretreated bladder, 1 heavily pretreated sarcoma), and three minimal responses (MRs) (pretreated sarcoma, bladder and prostate)."... ASCO 887 - 1999 Preliminary Results of a Two-Arm Phase 2 Trial of Gemcitabine (Gem) in Patients (Pts) with Gastrointestinal Leiomyosarcomas (leios) and Other Soft-Tissue Sarcomas (STS). Two groups: 14 GI leios and 16 other STS. STS: 1 CR (angiosarcoma), 2 PRs (uterine leios), and 1 MR (extremity leio)= 4/16 RR. TTP is 9+ mo for the CR and 4+ and 5 mo for the PRs. GI leio : 1 mixed response. ASCO 2091 - 1999 Gemcitabine in Patients with Sarcoma of Soft Tissue or Bone Resistant to Standard Chemotherapy. "Objective responses were minimal to partial in 2/13 (STS: Angiosarcoma, leiomyosarcoma) stabilization in 3/13 (BS). Time to progression was 4--45(+) w, median 8(+)w. Conclusions:gemcitabine is worth-studying in patients with sarcomas, refractory to standard chemotherapy." ASCO 2098 - 1999 Severe Nonhematologic Toxicity After Treatment with Gemcitabine. Discussion of cardiac and pulmonary toxicity with Gemcitabine. ASCO 2313 - 1999 GEMCITABINE (GEM) IN PRETREATED PATIENTS WITH ADVANCED SOFT TISSUE SARCOMAS (STS) ---PRELIMINARY RESULTS FROM A PHASE II TRIAL. "According to recent preliminary data prolonged infusion of GEM might be superior to the brief 30-minute infusions that have been used in most phase IItrials (J Clin Oncol 15:2172, 1997). " "Using GEM (200 mg/m2) as a 360-minute infusion on days 1, 8, 15 of a 28 day cycle in heavily pretreated pts with advanced STS". Ten pts evaluable for response produced 2 partial remissions and 3 SD. ASCO 1976 - 1998 compiled by doctordee updated October 2003

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