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Chemotherapy

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Overview

8/12/02 Preventing Chemotherapy Toxicities And Other Issues On Drugs Used In Oncology
6/20/01 Patients and physicians often disagree on the goal of chemotherapy May 16 2001 Reuters. Cancer patients are more likely to expect that a cure is the goal of chemotherapy, while physicians are more likely to consider palliation to be the goal of chemotherapy, according to the results of a new survey presented at the annual meeting of the American Society of Clinical Oncology. Overall, the investigators found that patients and physicians agreed on the goal of chemotherapy less than half of the time.
7/17/01 New drug may help with resistant cancers Tuesday, Jul 17 2001 In laboratory studies on ovarian and colon cancer cells scientists at the Beatson Laboratories at Glasgow University found that the drug decitabine, produced by US pharmaceutical company SuperGen Inc., made the cells more sensitive to chemotherapy drugs.
6/20/01 Side Effects of Chemotherapy: Anemia Medscape (registration required) Medscape's 'Side Effects of Chemotherapy: Anemia' Resource Center is a collection of the latest medical news and information on the prevention, diagnosis and therapy of chemotherapy-associated anemia
9/18/01 CENTER FOR MOLECULAR MEDICINE SPECIAL PROTOCOLS III Treatment of Colon Cancer Metastatic to the Liver. Dr. Order's protocol for the treatment of colon cancer metastatic to the liver targets patients who have failed conventional chemotherapy. On a selective basis, dictated by the geometry of the cancer, he uses three modalities (external radiatio n, chemoembolization, and colloidal P-32). The sequence is based on the patient's presentation. Phase 2 studies reveal that survival has been extended for one year or more in all patients undergoing these therapies, while maintaining quality of life.
9/18/01 A TAILORED PLAN (USC/Norris Comprehensive Cancer Center) A genetics-based diagnostic technology allows oncologists to better determine which cancer treatment will work best against a patient's specific cancer When physicians discover a patient has a cancerous tumor, they surgically remove it or remove a portion for a biopsy before starting chemotherapy or radiation. Under the new service, physicians can send a sample of the tumor tissue to the laboratory for advanced analysis. This allows physicians to incorporate valuable information into their decisions and helps them recommend the most effective treatment for a patient's specific cancer "Kathleen and Peter Danenberg have developed a method that allows for the examination of gene expression in a single tissue section," says Lenz, who has treated hundreds of patients with gastrointestinal cancers and performs research on cutting-edge therapies. "This will revolutionize the way we can screen for chemoresistance." What it means for physicians is that cancer treatments can be tailored to best fit with each patient's genetic makeup. The USC researchers have identified important genetic markers in tumor tissue that can predict which tumors will respond best to certain types of chemotherapy. The chemotherapeutic agents currently being used are 5-FU (fluorouracil) and cisplatin, which are often given for colon, lung, pancreatic and stomach cancer, as well as other cancers
11/06/01 OncoLink FAQ: Blood Counts Why does chemotherapy affect my blood counts?
7/15/02 Advances in Colorectal Cancer: How Much Progress Have We Made? John S. MacDonald, MD ASCO 2002

5-FU
10/27/01 5-FU Medline Plus Drug Information
10/27/01 5-FU BC Cancer Agency
10/27/01 5-FU Nurses PDR
10/27/01 Common Toxicity of Chemotherapy
10/27/01 Photosensitizers
10/27/01 5-Fu and St Johns Wort
10/27/01 Side Effects to Chemotherapy Drugs

Xeloda
6/23/01 Xeloda.com Homepage
10/9/01 Xeloda Label
10/9/01 Xeloda Roche Pharmaceuticals
10/9/01 Xeloda BC Cancer Agency
5/10/01 The Journal of Clinical Oncology Publishes Phase III Clinical Study Using Roche's Oral Chemotherapy Xeloda -Capecitabine- for Metastatic Colorectal Cancer April 16, 2001 first-line treatment of metastatic colorectal cancer (
5/17/01 Roche Receives U.S. Approval for Xeloda in Metastatic Colorectal Cancer "Smart Tablet" Offers Patients Superior Anti-tumour Activity, Improved Safety and Convenience May 2, 2001
5/17/01 FDA Approves Hoffmann-La Roche's Xeloda(R), First Oral Chemotherapy For The Treatment Of Metastatic Colorectal Cancer
6/20/01 Oral chemotherapy saves resources and time Reuters. A major shift from intravenous to the newer forms of oral chemotherapy for colorectal and other cancers will occur because of patient preference and because the potential cost savings are substantial, a specialist told a workshop here at the third International Perspectives in Colorectal Cancer Conference.
4/15/01 Zolota is a new medication, tested by M.D. Anderson Cancer Center. Oral Chemo Pill April 12, 2001
4/13/01 Chemotherapy pill causes fewer side effects April 13, 2001 CNN Medical Unit Capecitabine, Xeloda - Oral Chemo Pill was approved as an oral chemotherapy drug for breast cancer in 1998. The research appears in the April 15 issue of the Journal of Clinical Oncology MD Anderson Cancer Center
8/30/01 A Phase II Study of Xeloda (Capecitabine) in Patients with Metastatic Colorectal Cancer Demonstrating Progression on 5-FU Therapy Our preliminary data showed no objective responses with the use of capecitabine in patients who have failed treatment with i.v. bolus 5-FU. Disease stabilization, however, was seen in a noticeable number of patients. Of the 19 eligible and evaluable patients, the median number of treatment cycles was 3 (range 1-8). Six of 19 (32%) patients experienced disease stabilization for ł6 cycles. Seventeen patients withdrew due to progressive disease and 4 patients withdrew due to adverse events (3 due to increased bilirubin and 1 due to an acute thromboembolic event). No objective responses were observed
9/1/01 Improving Therapy of Colorectal Cancer With New Agents Medscape Article - Registration Required. Xeloda vs IV 5-FU
9/1/01 The Role of Oral Fluoropyrimidines in the Treatment of Breast and Colorectal Cancer Medscape Article - Registration Required
9/20/01 A Phase III Trial of XELODA TM (Capecitabine) in Previously Untreated Advanced/Metastatic Colorectal Cancer ASCO 1999 The overall best response rates were 23.2% (1.3% CR) vs 15.5% (1.0% CR) in the capecitabine and Mayo arms, respectively (p=0.02). The duration of response (9.1 vs 9.7 months) and progression-free survival (4.4 vs 5.1 months) were similar in both treatment arms. Survival data is immature at this time. Serious AEs occurred in 13.4% of the patients treated with capecitabine vs 23.1% in the 5-FU/LCV arm
9/20/01 Continuous Low-Dose Capecitabine Produces Significant Biochemical Responses in Patients with Progressive Gastroenteropancreatic (GEP) Neoplasms ASCO 2001 We hypothesized that low-dose continuous capecitabine, an oral 5-FU prodrug, would be well tolerated and may decrease biochemical markers in patients with GEP neoplasms. To test this hypothesis, 42 patients (pts) with progressive metastatic GEP neoplasms, including carcinoid and pancreatic islet cell carcinomas, received capecitabine (1,000-2,500 mg/d) for 60 days Seven pts (41.2%) experienced an objective partial biochemical response (50% or greater reduction) and 7 pts had stable disease (less than 50% reduction)
9/20/01 Human Thymidylate Synthase Gene Polymorphism Determines Response to Capecitabine Chemotherapy in Advanced Colorectal Cancer ASCO 2001 We found that 80% (4/5) of individuals with the S/S variant responded to capecitabine, compared to 10% (1/10) and 14% (1/7) of those with the S/L and L/L variants respectively (p=0.026 Fisher's exact test.) It is our conclusion that genotyping patients for the TS polymorphism may be useful in identifying patients who are more likely to respond to capecitabine treatment for advanced colon cancer
9/20/01 A Retrospective Evaluation of the Impact of Dose Reduction in Patients Treated with Xeloda (Capecitabine). ASCO 2000 Results show that dose reduction had no effect on achieving a response, duration of response, time to treatment failure (TTF) or survival. Among pts who responded prior to vs after dose reduction, there was little difference in duration of response (201 vs 263 days), TTF (213 vs 263 days) and survival time (331 vs 393 days). Our results show that the dose of capecitabine can be reduced to minimize toxicity without compromising efficacy
9/20/01 A Phase II Study of Xeloda (Capecitabine) in Patients with Metastatic Colorectal Cancer Demonstrating Progression on 5-FU Therapy ASCO 2000 Of the 19 eligible and evaluable patients, the median number of treatment cycles was 3 (range 18). Six of 19 (32%) patients experienced disease stabilization for ?6 cycles. Seventeen patients withdrew due to progressive disease and 4 patients withdrew due to adverse events (3 due to increased bilirubin and 1 due to an acute thromboembolic event). No objective responses were observed
9/20/01 Characterizing Hand-Foot Syndrome (HFS) Caused by Capecitabine ASCO 2000 The first, and the worst, episode of HFS developed within the first 2 cycles in 92.8% and 67.8% of the patients respectively. The only significant association was with better performance status (PS), i.e. better PS was associated with higher frequency of HFS (P=0.038 after adjusting for number of cycles). The proportions of patients having HFS were relatively constant along subsequent cycles. HFS led to dose reduction in 16 patients, but none of our patients required drug discontinuation due to HFS.
9/20/01 Xeloda in colorectal cancer. Int J Clin Pract 2001 Jun;55(5):326-328 Cassidy J. Phase I and II trials were performed in colorectal cancer to define the optimal dose and schedule of capecitabine. In two large scale phase III studies this agent has been shown to be at least as effective as a standard regimen of bolus 5-FU and leucovorin (Mayo regimen). Response was superior in the capecitabine arms of these studies with equivalence of progression-free and overall survival
1/21/02 Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study J Clin Oncol 2001 Nov 1;19(21):4097-106 CONCLUSION: Oral capecitabine achieved an at least equivalent efficacy compared with IV 5-FU/LV. Capecitabine demonstrated clinically meaningful safety advantages and the convenience of an oral agent.

Camptosar (also called Irinotecan, CPT-11)
5/01/01 Pharmacology of Camptothecin, Irinotecan and Topotecan (oxaliplatin-article by cancerconsultants.com)
6/20/01 Unexpectedly high mortality rate associated with chemotherapy regimen May 18, 2001 Reuters Researchers have detected a higher than expected fatality rate associated with an irinotecan, fluorouracil and leucovorin regimen that is approved by the US Food and Drug Administration for colorectal cancer
7/24/01 Camptosar Information from Meds.com - includes package insert
7/24/01 Camptosar Package Insert Latest from Pharmacia - can download Adobe Acrobat reader here also to read insert
10/3/01 Irinotecan-associated pulmonary toxicity Madarnas Y, Webster P, Shorter AM, Bjarnason GA Anticancer Drugs 2000 Oct;11(9):709-13 Progressive pulmonary insufficiency and death were reported in the initial Japanese studies, despite institution of empiric steroid therapy for a syndrome similar to that which our patient experienced. As a result, patients with compromised pulmonary function were generally excluded from US clinical trials. Notwithstanding this, cough and dyspnea were reported in approximately 20% of patients in the US studies. As the clinical indications for the use of this agent expand, we describe irinotecan-associated interstitial pneumonitis as a serious potential adverse effect. Patients with pre-existing pulmonary disease may be at higher risk for this complication and clinicians should be alert to this possibility.
10/3/01 Mortality Associated With Irinotecan Plus Bolus Fluorouracil/Leucovorin: Summary Findings of an Independent Panel J Clin Oncol 2001 Sep 15;19(18):3801-7 Rothenberg ML, Meropol NJ, Poplin EA, Van Cutsem E, Wadler S. The inpatient, outpatient, and research records of patients treated on Cancer and Leukemia Group B protocol C89803 and on North Center Cancer Treatment Group protocol N9741 were reviewed by a panel of five medical oncologists not directly involved with either study. Each death was categorized as treatment-induced, treatment-exacerbated, or treatment-unrelated. RESULTS: The records of 44 patients who experienced early deaths on C89803 (21 patients) or N9741 (23 patients) were reviewed. Patients treated with irinotecan plus bolus 5-FU/leucovorin had a three-fold higher rate of treatment-induced or treatment-exacerbated death than patients treated on the other arm(s) of the respective studies Multiple gastrointestinal toxicities that often occurred together were characterized into a gastrointestinal syndrome. Sudden, unexpected thromboembolic events were characterized as a vascular syndrome. The majority of deaths in both studies were attributable to one or both of these syndromes. CONCLUSION: Close clinical monitoring, early recognition of toxicities and toxicity syndromes, aggressive therapeutic intervention, and withholding therapy in the presence of unresolved drug-related toxicities is recommended for patients receiving IFL or other intensive chemotherapy regimens.
10/3/01 Irinotecan and radiation in combined-modality therapy for solid tumors. Oncology (Huntingt) 2001 Jul;15(7 Suppl 8):22-8 Choy H, MacRae R. The increasing amount of data demonstrating improved outcomes with concurrent chemoradiation treatment of malignancies like lung cancer and head and neck cancer provide impetus for pursuing the addition of other drugs as radiosensitizers to improve local control further. Irinotecan is undergoing early clinical trials in the combined-modality setting in several disease sites. This article will provide an overview of the current status of irinotecan used concurrently with radiotherapy in the treatment of a variety of solid tumors
7/3/01 Irinotecan plus Fluorouracil and Leucovorin for Metastatic Colorectal Cancer Leonard B. Saltz, M.D., John V. Cox, D.O., Charles Blanke, M.D., Lee S. Rosen, et al. Source: New England Journal of Medicine Sept 28, 2000 Abstract: In a multicenter trial, we compared a combination of irinotecan, fluorouracil, and leucovorin with bolus doses of fluorouracil and leucovorin as first-line therapy for metastatic colorectal cancer. A third group of patients received irinotecan alone. Notes: This was the paper that established Camptosar, fluorouracil, leucovorin as the new standard "first line" therapy for colon cancer
7/3/01 Colon Cancer Treatment May Be More Toxic Than Thought Triple-Drug Therapy Causes Severe Side Effects, Death By Andrea Braslavsky WebMD Medical News May 17, 2001 According to a letter to the editor that was slated to appear in the June 21 issue of The New England Journal of Medicine, two separate studies show a chemotherapy regimen combining the recently approved Camptosar with two well-known drugs -- 5-FU and Leucovorin -- caused an unexpectedly high number of deaths within 60 days of starting treatment. In the letter, O'Connell and three other researchers write that in the North Central Cancer Treatment Group trial, 14 colon cancer patients who received the three-drug combination died, compared with five patients in each of two other medication arms. In the second trial, by the Cancer and Leukemia Group B cooperative group, 14 patients who received the triple combination died, compared with five patients in another medication group. New patient enrollment in the two trials, both sponsored by the National Cancer Institute, has been suspended, and patients receiving the triple-drug combination have had their medication doses modified to reduce the toxic effects of the treatment.
7/3/01 Unexpectedly high mortality rate associated with chemotherapy regimen Friday, May 18 2001 Researchers have detected a higher than expected fatality rate associated with an irinotecan, fluorouracil and leucovorin regimen that is approved by the US Food and Drug Administration for colorectal cancer.
7/21/01 Thalidomide May Ease Cancer Treatment Chemo side effects appear weakened by drug WEDNESDAY, Aug. 16 2000
7/21/01 2191 Irinotecan and Thalidomide in Metastatic Colorectal Cancer: Preliminary Results of a Phase II Study. ASCO 2001 Thalidomide appears to decrease GI toxicity associates with Irinotecan (Camptosar, CPT-11) There was a remarkable decrease in the observed vs. expected gastrointestinal toxicities(table). Fourteen patients who received at least two cycles of irinotecan did not require dose reduction. Conclusions: Thalidomide improves the tolerability of irinotecan by decreasing the gastrointestinal toxicities. The response rates appear to be greater in the pilot study which is being studied in this ongoing phase II study.
9/22/01 A Phase I and Pharmacokinetic (PK) Trial of Oral Formulation of Irinotecan Administered Daily for 14 Days Every 3 Weeks in Patients (pts) with Solid Tumors. ASCO 2001 Abstract Dose limiting toxicities (DLT) observed at cycle 1 consisted of reversible grade (gr) 4 diarrhea in 2/2 pts treated at 35 mg/m˛/d, and gr4 diarrhea or gr3 vomiting in 3/5 pts treated at 40 mg/m˛/d. Myelosuppression was minimal with neither gr3 nor gr4 neutropenia or thrombocytopenia. One partial response (colon cancer) was observed (17.5 mg/m˛/d) and disease stabilization was noted in 11 pts

Oxaliplatin
8/22/02 Colorectal Cancer Drug Provides Important Option For Patients With Advanced Disease The U.S. Food and Drug Administration announced today that it had approved oxaliplatin to treat patients whose metastatic colorectal cancer has progressed after standard chemotherapy. The approval was based on data from a multi-center trial in the U.S. and Canada, led by Dr. Mace L. Rothenberg, which demonstrated that adding oxaliplatin to standard chemotherapy was better than either one alone at shrinking tumors and keeping them in check.
8/12/02 ELOXATIN Chemotherapy for Advanced Colorectal Cancer, Receives Approval from the U.S. Food and Drug Administration The NDA submission of ELOXATIN was based on results of a U.S. and Canada multicenter, randomized, controlled study comparing the safety and efficacy of ELOXATIN in combination with infusional 5-FU/LV with that of infusional 5-FU/LV alone and that of ELOXATIN alone. The clinical trial included 463 randomized patients with advanced colorectal cancer whose disease had relapsed or progressed either while taking or within six months of therapy with bolus 5-FU/LV + irinotecan. Accrual to this study has been completed with 821 patients enrolled. The confirmed objective tumor response rates defined as a 30% or greater reduction in overall tumor size, maintained for 4 weeks or more were 9.0% for the ELOXATIN in combination with infusional 5-FU/LV group (n=152), compared with 0% for the infusional 5-FU/LV alone (n=151), p=0.0002 and 1% for ELOXATIN alone group (n=156). The median time to tumor progression with ELOXATIN in combination with infusional 5-FU/LV was 4.6 months, compared with 2.7 and 1.6 months for infusional 5-FU/LV alone and ELOXATIN alone, respectively. This represents a 2 month increase in median time to progression compared to infusional 5-FU/LV alone.
8/13/02 Colorectal Cancer Drug Provides Important Option For Patients With Advanced Disease Specifically, the tumor response rate was 9 percent among patients receiving the combination therapy compared to 0 percent and 1 percent for 5FU/leucovorin alone and oxaliplatin alone. Tumor response is defined as the proportion of patients whose tumors shrank by at least 30 percent and whose shrinkage lasted for at least four weeks.
8/13/02 The FDA Redefines "Fast" Editorial
7/15/02 New Therapeutic Options in Colon Cancer - Focus on Oxaliplatin CJON Vol 6 #3 May/June 2002
7/15/02 Eloxatin Product Information from Sanofi - I guess this will be the "Package Insert" when Oxal is approved by the FDA (?)
6/5/02 Experimental and Unconventional Search on Oxaliplatin
6/5/02 New Drug Regimen Shows Clear Benefit for Treating Advanced Colorectal Cancer Saturday, May 18, 2002 Initial results from a large, randomized clinical trial for patients with advanced colorectal cancer show that those who received a regimen containing the investigational drug oxaliplatin lived months longer than those who received a standard therapy. Patients on the oxaliplatin regimen, known as FOLFOX4, also had a longer time before their tumors progressed, a better response rate, and fewer severe side effects.
6/5/02 NCI Digest Page: Oxaliplatin
7/15/02 BB Post - Oxaliplatin
7/15/02 A multivariate analysis of genetic markers for clinical response to 5-FU/oxaliplatin chemotherapy in advanced colorectal cancer ASCO 2002 Abstract 513 Among the genetic polymorphisms tested, we found that XPD Lys751Lys, ERCC1-19007 C/C, and GSTP1 Val/Val polymorphisms were significant independent predictors of improved clinical outcome to chemotherapy (p=0.010-0.027). In the subsequent multivariate analysis of these three genes, the relative risk of dying increased 2-3 times for patients that lacked the beneficial genotype in one or more genes (p<0.001). This association remained true even when such prognostic indicators as overall performance status (ECOG) and tumor side were taken into account in the analysis. Conclusion: The XPD751, ERCC1-19007, and the GSTP1 polymorphisms may be powerful genetic markers that may predict clinical response to 5-FU/oxaliplatin
11/08/01 Oxaliplatin - BC Cancer Agency
11/08/01 Oxaliplatin side effects
11/08/01 Oxaliplatin A new chemotherapy drug that is emerging in the fight against colorectal cancer is oxaliplatin (Eloxatine(r)). Oxaliplatin, widely available in Europe, Asia, and Latin America, is being studied in the U.S. Common side effects of oxaliplatin are nerve pain in the hands and feet (neu- ropathy), vomiting, diarrhea, and neutropenia
4/20/01 Important Clinical Trial Begins for Patients with Advanced Colon Cancer (oxaliplatin-article by cancerconsultants.com)
9/1/01 Oxaliplatin: Shows Efficacy in Metastatic Colorectal Cancer and Has Potential for the Treatment of Other Malignancies Medscape Article - Registration Required. Objective response rates of 50% have typically been achieved for first-line therapy and of 13 to 45% for second-line therapy. Furthermore, treatment with this combination has enabled the surgical removal of previously unresectable liver metastases
9/1/01 Use of the New Chemotherapy Drugs Oxaliplatin and Capecitabine in the Treatment of Solid Tumors Phase I Pilot Study of Oxaliplatin in Combination with Capecitabine in Patients with Solid Tumors. . Like oxaliplatin there is interest in studying its effect in other forms of cancer. In this study, the plan is to combine these two promising chemotherapy drugs and use them to treat solid cancers that have failed conventional therapy. The hope is that the combination of these two drugs will give a good anti-tumor response with an acceptable side effect profile
9/1/01 Use of the New Chemotherapy Drug Oxaliplatin in the Treatment of Metastatic Colon or Rectal Cancer. A Compassionate Use Study of Oxaliplatin For Previously Treated Colorectal Cancer Patients Previously Treated Patients. Oxaliplatin is a new chemotherapy drug. In a number of clinical trials, it has shown much promise for the treatment of colon and rectal cancer with a reasonable side effect profile. This drug is now being offered by Sanofi Pharmaceuticals for compassionate use for patients with metastatic colon or rectal cancer that has failed other chemotherapy drugs. The trial is available in a number of hospitals around the country, while it awaits a formal review by the Food and Drug Administration (FDA).
9/10/01 oxaliplatin from Cancerbacup.org (UK site)
6/16/01 Steven Parr's Homepage Steven Parr is a Stage IV colon cancer survivor from England. He was first diagnosed in March, 1996. He is currently (sept 2001) on oxaliplatin chemotherapy and tells about his experiences With it here.
1/21/02 [Prevention of oxaliplatin-induced neuropathy by carbamazepine: A pilot study] Dtsch Med Wochenschr 2002 Jan 18;127(3):78-82 CONCLUSIONS: These observations demonstrate that oxaliplatin-induced sensory neuropathy more than grade 1 may be prevented by carbamazepine. Prevention of oxaliplatin-induced neurotoxicity by carbamazepine would possibly enable chemotherapy with considerable higher doses of oxapliplatin and thus enhance activity. A multicenter trial will elucidate if more serious distal neurotoxicities, which occur after application of higher cumulative doses of oxaliplatin, can also be prevented by carbamazepine

Cisplatin

Cisplatin appears to have some interest as a colon cancer therapy in Japan, but all I could find was some "anecdotal" type articles by Japanese researchers. Oxaliplatin is a "cisplatain analogue" and is apparently believed to to be better than cisplatin for Colorectal cancer. The writeup for one Oxaliplatin clinical trial said "Oxaliplatin is a new chemotherapy drug tested extensively in France but not yet approved in the United States. This drug is similar to a standard chemotherapy drug called cisplatin but has much more activity in colon cancer" Another article said there may be "oxaliplatin activity in some cisplatin-resistant tumours".
9/15/01 Cisplatin Info for Health Professionals (British Columbia Cancer Agency)
Cisplatin produces moderate to severe nausea and vomiting in virtually all patients. Nausea and vomiting may start within one hour and last up to 24 hours. Tolerance improves with IV hydration and 5-day continuous infusion. Various degrees of nausea and anorexia may persist for up to 1 week. The use of prophylactic and continuing antiemetic medication is recommended. Neurotoxicity consists of peripheral neuropathies which are sensory in nature but can also include motor difficulties, reduced deep-tendon reflexes and leg weakness. Symptoms usually occur after prolonged therapy (4-7 months) and may be irreversible. Seizures, altered taste, slurred speech, and memory loss have occurred rarely. Cisplatin should be discontinued if functionally important neuropathy develops. Ototoxicities consist of audiogram abnormalities in 24% of patients. Auditory impairment usually results in impairment of acuity in the high frequency range, but may affect the normal hearing range in 6% of cases. Ototoxicity is cumulative, dose-related and irreversible. The occurence of clinical hearing loss is 6% and tinnitus 9%. Hearing loss may be more severe in children. Cranial irradiation may lower the cumulative dose at which cisplatin will cause hearing loss, although one group of investigators found no increase in ototoxicity when cisplatin was given before, instead of following, cranial irradiation. Vestibular ototoxicity is rare. Pure-tone threshold audiometry (or auditory brainstem response in young children) should be done before the first dose of cisplatin, after the first dose and at regular intervals thereafter, especially after a cumulative dose of 360 mg/m˛ has been reached.
9/15/01 Cisplatin- toxicity
9/15/01 Cisplatin for Injection
9/15/01 Cisplatin (Systemic) info from medlineplus
9/15/01 OncoLink Chemotherapy Drug Reference: Cisplatin
9/15/01 [A case of metastatic colon carcinoma in which a continuous intrahepatic artery-infusion of 5-FU leucovorin and cisplatin, and systemic chemotherapy with CPT-11 was very effective]. Gan To Kagaku Ryoho 2000 Aug;27(9):1443-1447 Ishikawa T, Nakamura M, Ohkuma K, Hisano C, Nakano S, Maruyama T, Kaji Y, Niho Y, Masumoto N. We report a patient with metastatic colon carcinoma who was treated effectively with a continuous intrahepatic artery-infusion of 5-FU, Leucovorin and cisplatin, and systemic chemotherapy with CPT-11
9/15/01 Basis for effective combination cancer chemotherapy with antimetabolites. Pharmacol Ther 2000 Aug;87(2-3):227-253 Peters GJ, van der Wilt CL, van Moorsel CJ, Kroep JR, Bergman AM, Ackland SP Other combinations, currently frequently used in the treatment of solid malignancies, include an antimetabolite with a DNA-damaging agent, such as gemcitabine with cisplatin and 5FU with the cisplatin analog oxaliplatin
9/15/01 Double cancer (lung and colon cancer) that showed complete remission with irinotecan and cisplatin combined chemotherapy. J Gastroenterol 2000;35(11):864-869 Kaneki T, Koizumi T, Kawashima A, Tsushima K, Kubo K, Fujimoto K, Honda T, Akamatsu T. We report a rare case of double (colon and lung) cancer which showed complete remission with chemotherapy with irinotecan (CPT-11) and cisplatin (CDDP).
9/15/01 Three cases of liver metastasis of colon cancer responding to systemic combination chemotherapy utilizing CPT-11]. Gan To Kagaku Ryoho 2000 Dec;27(14):2255-2258 Kobayashi A, Yamaguchi M. In the present paper, we report 3 cases of effective systemic chemotherapy utilizing CPT-11 for liver metastases from colon cancers. The method was UFT + irinotecan (CPT-11), cisplatin (CDDP) + tegafur + CPT-11, UFT + CPT-11 + etoposide (ETP) + pirarubicin (THP). The result obtained was a partial response (PR) in each case. As there were few adverse effects, we could provide treatment during a short-term admission or an outpatient basis
9/15/01 Biweekly low-dose cisplatin and 5-fluorouracil combination chemotherapy for advanced gastrointestinal carcinoma]. Gan To Kagaku Ryoho 2000 Jun;27(6):859-864 Kamata T, Morita A, Nakamoto A, Onishi I, Takeda T, Koyasaki N, Kanno M. Biweekly intravenous infusions of low-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) were evaluated in 80 patients with advanced or recurrent gastric, colorectal, pancreatic or gallbladder adenocarcinoma The response rate among patients with gastric cancer was 26%, colorectal cancer 10%, pancreatic cancer 7.7%, and gallbladder cancer 42.9%. The response rates were not so high, but the median survival time of patients with recurrent gastric cancer was 17.3 months, pancreatic cancer 6.7 months, and gallbladder cancer 10.7 months
9/15/01 Chronomodulated infusion of cisplatin, 5-fluorouracil and folinic acid: lack of activity in advanced colorectal cancer. Anticancer Res 2000 Mar;20(2B):1253-1256 Natoli C, Scognamiglio MT, Martino MT, Irtelli L, De Tursi M, Cianchetti E, Mascitelli E, Tinari N, Iacobelli CONCLUSIONS: The results of this study discourage the substitution of cisplatin for the more active compound, oxaliplatin, in a chronomodulated schedule of infusion with 5-FU and FA in patients with metastatic colorectal cancer
9/15/01 [Combination chemotherapy of continuous infusion 5-FU and daily low-dose CDDP in colorectal carcinoma]. Gan To Kagaku Ryoho 1999 Oct;26(11):1554-1558 Furuhata T, Hirata K, Yamamitsu S, Kimura H, Sasaki K, Hata F, Shirasaka T. Continuous intravenous infusion (CVI) of 5-fluorouracil (5-FU) plus daily low-dose cisplatin (CDDP) was evaluated in 59 patients with advanced and unresectable colorectal carcinoma. We concluded that low-dose FP and intermittent FP therapy might be fairly effective for advanced and unresectable colorectal carcinoma.
9/15/01 [Clinical evaluation of intermittent hepatic arterial infusion therapy with CDDP and 5-FU for liver metastasis of colorectal cancer]. Gan To Kagaku Ryoho 1999 Oct;26(12):1715-1717 Miya K, Saji S, Fukada D, Umemoto T, Kunieda K, Sugiyama Y, Takao H, Kato M, Kawaguchi Y Twenty-seven patients with liver metastasis from colorectal cancer were treated with intermittent intra-arterial infusion chemotherapy for 5 years starting from 1993. . Five to ten mg of CDDP, 250 mg of 5-FU and/or 3-6 mg of Leucovorin were administered weekly
9/15/01 A randomised phase II study of oxaliplatin alone versus oxaliplatin combined with 5-fluorouracil and folinic acid (Mayo Clinic regimen) in previously untreated metastatic colorectal cancer patients. Eur J Cancer 2001 May;37(8):1006-1013 Zori Comba A, Blajman C, Richardet E, Bella S, Vilanova M, Coppola F In conclusion, oxaliplatin at a dose of 85 mg/m(2) given every 2 weeks was well tolerated and has limited activity in metastatic CRC, while the combination of this treatment with the full-dose Mayo clinic regimen (5-FU bolus 425 mg/m(2)/day+FA 20 mg/m(2)/dayx5 days every 4 weeks), although active, was unfeasible due to a high level of myelosuppression and gastrointestinal toxicity. Alternative lower dosing or other regimens are to be explored to ascertain the value of bolus 5-FU/FA combined with oxaliplatin
9/15/01 Ongoing and unsaid on oxaliplatin: the hope. Br J Cancer 1998 Jun;77Human:8-11 Cvitkovic E. Ongoing molecular pharmacological studies of the mechanism of action of cisplatin suggest that platinated adducts are recognized by proteins of the mismatch repair system, including the products of the hMLH1 and hMSH2 genes. DNA mismatch repair defects occur in a wide variety of sporadic human cancers, are the main genetic factor in hereditary non-polyposis colon cancer and a frequent de novo or acquired phenomenon in ovarian cancer and other solid tumours. Moreover, they have recently been reported to be a cause of resistance to cisplatin but not to oxaliplatin, as diaminocyclohexane platinum adducts do not appear to be recognized by the mismatch repair complex. These findings explain the oxaliplatin activity in some cisplatin-resistant tumours.
9/15/01 Story of Survivor - Used Cisplatin
9/15/01 Phase II Study of Oxaliplatin with Weekly 5-FU Leucovorin for Colon Cancer Oxaliplatin is a new chemotherapy drug tested extensively in France but not yet approved in the United States. This drug is similar to a standard chemotherapy drug called cisplatin but has much more activity in colon cancer

Chemoembolization
9/18/01 Chemoembolization Dept of Surgery, Beth Israel Medical Center (Harvard)
ENTERED 9/18/01 CENTER FOR MOLECULAR MEDICINE SPECIAL PROTOCOLS III Treatment of Colon Cancer Metastatic to the Liver. Dr. Order's protocol for the treatment of colon cancer metastatic to the liver targets patients who have failed conventional chemotherapy. On a selective basis, dictated by the geometry of the cancer, he uses three modalities (external radiation, chemoembolization, and colloidal P-32). The sequence is based on the patient's presentation. Phase 2 studies reveal that survival has been extended for one year or more in all patients undergoing these therapies, while maintaining quality of life.
9/22/01 Information about Chemoembolization
9/22/01 Penn Researchers Find Chemoembolization Effective for Liver Tumors
9/22/01 Chemoembolization
9/22/01 Chemoembolization Five months later the tumor was necrotic (depicted as a round and homogenous mass) and the remainder of the liver had grown or hypertrophied. This patient subsequently underwent a liver resection.
9/22/01 SCVIR MEETING: Chemotherapy Delivered Directly to Liver Tumours Doubles Life Expectancy PHILADELPHIA, PA -- March 24, 1999 In this study, 51 patients whose colon cancer had metastasised to the liver were treated with chemoembolization. Eighty-six percent, or 44 of the patients, survived one year after treatment. The patients in this study survived an average of two years. Typically, less than half of liver cancer patients survive one year after undergoing systemic chemotherapy
9/22/01 Preoperative Chemoembolization of Hepatocellular Carcinoma A Comparative Study Archives of Surgery 1998 Conclusions Convincing evidence is lacking to support systematic preoperative CE in patients with initially resectable hepatocellular carcinoma. Further studies should aim to identify the subgroup of patients who may benefit from this neoadjuvant treatment

Mitomycin
9/28/01 5-fluorouracil modulated by leucovorin, methotrexate and mitomycin: highly effective, low-cost chemotherapy for advanced colorectal cancer Br J Cancer 2001 Apr 20;84(8):1023-8 Sobrero A, Guglielmi A, Cirillo M, Recaldin E, Frassineti GL, Aschele C, Ravaioli A, Testore P, Caroti C, Gallo L, Pessi MA, Cortesi E, Turci D, Grossi F, Labianca R. 105 patients with untreated, advanced, measurable colorectal cancer were accrued from 13 Italian centres and treated. 5 complete and 34 partial responses were obtained (response rate, 37% on the intention to treat basis; 95% confidence limits, 28-46%). After a median follow-up time of 26 months, 37 patients are still alive. The median progression-free survival is 7.7 months with an overall survival of 18.8 months and a 2-year survival rate of 30%. The regimen was very well tolerated with fewer than 13% of patients experiencing WHO grade III-IV toxicity

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