Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

One hundred and three patients previously treated with chemotherapy including an anthracycline were entered in a VMMC protocol study: vindesine (Eldisine), mitoxantrone (Novantrone) and mitomycin C (Ametycine). Group A consisted of 41 women who received the protocol published by Belpomme: vindesine (2.5 mg/m2 day 1 and 8) and mitoxantrone (12 mg/m2/day) every 4 weeks, and mitomycin C (8 mg/m2) every 8 weeks. Group B consisted of 62 patients who were treated with a modified protocol: vindesine (2.5 mg/m2) and mitoxantrone (12 mg/m2) every 3 weeks on day 1, and mitomycin C (8 mg/m2) every 6 weeks. Tolerance was acceptable with 79% of patients complaining of weakness. There was a 66% incidence of gastro-intestinal toxicity, a 10.7%-incidence of neurotoxicity (reversible dysethesias), and a 5.8% incidence of cardiotoxicity. There was considerable hematotoxicity of grade 2, 3 and 4: neutropenia 16.6%, thrombocytopenia 7.7%, anemia 21.4%. There was a 19.2% overall objective response rate (CR and PR) (95% confidence interval: 12-30) (CR: 3.2%). The median duration of the response was 39 weeks. There was no significant difference in response rates whether or not the patients (19 cases) were undergoing simultaneous hormonal therapy and no difference according to the protocol used. Similarly, neither menopause nor a previous response to anthracyclines had any effect on the response rate. The 19.2% response in this protocol is similar to other breast cancer salvage chemotherapy protocols for patients who have failed to respond to anthracyclines (< 20%).
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PMID:[A study of VMMC protocol (vindesine, mitoxantrone, mitomycin C) as a salvage chemotherapy in advanced breast cancers]. 139 55

A total of 56 heavily pretreated patients with advanced breast cancer were treated with the combination mitomycin and mitoxantrone. Partial responses were seen in ten of 56 patients (18%), or ten of 44 (23%) completing two courses, while 18 (32%) had stable disease. Responses were seen in eight patients failing doxorubicin. The median duration of response was 26 weeks, with responders surviving a median of 37 weeks. A total of 59% of the courses were associated with World Health Organization grade 3 or 4 neutropenia (less than 1.0 X 10(9) cells/L). Nausea and vomiting were minimal. Mitomycin and mitoxantrone has activity in heavily pretreated patients with advanced breast cancer.
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PMID:Mitomycin and mitoxantrone in previously treated patients with advanced breast cancer. 243 37

Between October 1980 and December 1985, 50 patients with esophageal cancer were treated with combined radiotherapy and chemotherapy (5-fluorouracil [5-FU] and mitomycin C). Thirty patients with stage I or II disease received definitive treatment consisting of 6,000 cGy in 6 to 7 weeks and 5-FU (1,000 mg/m2/24 h) as a continuous intravenous (IV) infusion for 96 hours, starting on days 2 and 29. Mitomycin C (10 mg/m2) was administered as a bolus injection on day 2. Twenty patients received palliative treatment (5,000 cGy plus chemotherapy) for stage III or IV disease (extraesophageal spread or distant metastases). All patients treated in this program had an Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2. Of the 30 definitively treated patients, 23 had squamous cell cancer, while seven had adenocarcinoma. Follow-up ranged from 6 months to 63 months. The complete response rate at 1 to 3 months following completion of treatment was 87% (26 of 30) documented by barium swallow and endoscopy (+/- biopsy). The actuarially determined local relapse-free rate at 1 year and beyond was 73%, and the actuarial survivals at 1, 2, and 5 years were 68%, 47%, and 32%, respectively. Of the 20 palliatively treated patients, ten had squamous cell carcinoma, eight had adenocarcinoma, and two had undifferentiated carcinoma. Seventeen patients were evaluable for freedom from dysphagia 1 or more months following completion of treatment. Eighty-two percent of evaluable patients (14 of 17) had no dysphagia posttreatment, while 64% (11 of 17) remained free of dysphagia until death or last follow-up, emphasizing the significant local control of those patients. The median survival for this group was 8 months. Treatment was well tolerated, and acute toxicity included esophagitis, stomatitis, oral candidiasis, and hematologic toxicities of thrombocytopenia and neutropenia. Late toxicities were predominantly manifested as a mild to moderate benign stricture, which required dilatation in four patients. One patient developed a perforation into the mediastinum in the absence of tumor, while two patients with persistent local disease developed tracheoesophageal fistula, and radiation pneumonitis was observed in two patients. This combination of radiation therapy with infusional 5-FU and mitomycin C is an effective and relatively well-tolerated regimen in the treatment of esophageal cancer. Surgical resection may not be necessary when high-dose radiation and chemotherapy are used.
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PMID:Nonsurgical management of esophageal cancer: report of a study of combined radiotherapy and chemotherapy. 244 31

An important objective of new anticancer drug discovery programs is identification of agents that are less myelosuppressive than those currently available. We have developed several animal models to evaluate these drugs for myelosuppression. Our screening model measures changes in neutrophil counts in mice as an indicator of myelosuppression. This model correctly predicted the myelosuppressive effects of 13 (76%) of 17 known agents. Cisplatin, carboplatin, spiroplatin, and marcellomycin caused no reduction in the neutrophil counts, representing four (24%) of 17 false negatives. Our secondary evaluation system is the more labor-intensive murine CFU-C assay on femoral bone marrow cells from drug-treated mice. Known myelosuppressive drugs such as mitomycin C, doxorubicin, and BCNU, as well as the false negatives from the mouse neutropenia model (cisplatin, carboplatin, spiroplatin, and marcellomycin) caused marked inhibition of colony formation 24 h after dosing; bleomycin was inactive. Advanced evaluations are performed using ferrets in which neutrophil counts can be monitored in the same animal for 28 days after treatment. Mitomycin C, doxorubicin, and BCNU caused significant reductions in the neutrophil counts whereas bleomycin had no effect. Importantly, cisplatin and marcellomycin also caused significant reductions in the neutrophil counts. Although the mouse neutropenia model is a rapid assay, there is potential for false-negative predictions. It is important that other test systems be used for more advanced evaluation of drugs identified by this model as being less myelosuppressive than reference drugs. The mouse CFU-C and ferret hematology models are suitable for this purpose in that they can identify the false-negative predictions as well as identify less myelosuppressive drugs such as bleomycin.
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PMID:Animal models for evaluating the myelosuppressive effects of cancer chemotherapeutic agents. 398 34

A 53-year-old man underwent chemotherapy (CDDP, VDS, MMC) for treatment of lung cancer. He was given 125 micrograms/m2 of GM-CSF subcutaneously every day for 8 consecutive days, in order to prevent neutropenia. Three days after starting GM-CSF therapy, marked eosinophilia in peripheral blood was observed. The maximum eosinophil count was 89% of leukocytes. Nine days after stopping the treatment with GM-CSF, the number of eosinophils had normalized spontaneously. There were no clinical symptoms except for slight fever, up to 37.5 degrees C. Moreover, there was no relationship between the number of eosinophils and the serum levels of cytokines (IL-3, IL-5, GM-CSF), although we observed minimal but significant elevation of serum ECP level. This case indicates that GM-CSF may induce marked eosinophilia rather than widely stimulating granulocytes and monocytes.
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PMID:[A case of marked eosinophilia in peripheral blood induced by rhGM-CSF]. 812 Oct 93

Mitomycin C (MMC)-vinblastine (VBL) is a regimen that has commonly been used as salvage therapy for advanced breast cancer for many years. The hematologic toxicity of this combination is one aspect that limits its usefulness. Amifostine, an organic thiophosphate, has been developed as a selective chemoprotective agent. In this pilot study, we tested the feasibility of MMC/VBL administration in combination with amifostine and we monitored the hematologic toxicity closely. Patients having failed one or two chemotherapy regimens for advanced breast cancer, with a good performance status scored at 2 or better and measurable or evaluable lesion(s), were eligible. They were treated according to the following schedule: mitomycin C 10 mg/m2 i.v. day 1, vinblastine 5 mg/m2 i.v. day 1 and 15, amifostine 910 mg/m2 in short i.v. infusion prior to MMC. Premedication consisted of dexamethasone 3 x 20 mg, haloperidol 2 x 0.5 mg p.o., hydration with 11 of normal saline, metoclopramide 1.5 mg/kg in short infusion and procyclide HCl 10 mg i.v. Cycles were repeated every 4 weeks. In all, 14 cycles were administrated to six heavily pretreated patients. Following the first cycle, five of the six patients experienced grade 3 or 4 neutropenia on day 15, and consequently did not receive the second vinblastine administration as planned. Three out of four patients receiving two or more cycles had moderate thrombocytopenia. There were no patients with neutropenic fever or major bleeding problems. The MMC/VBL+amifostine regimen was well tolerated regarding other toxicities. Neither amifostine-related acute vomiting nor any significant decrease in blood pressure was observed. Administration of amifostine in combination with MMC/VBL was feasible but in this group of heavily pretreated patients there were no hints of a protective effect of amifostine on the hematologic toxicity profile of this chemotherapy regimen.
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PMID:Mitomycin C and vinblastine in combination with amifostine in metastatic breast cancer. A feasibility study of the EORTC--Investigational Drug Branch for Breast Cancer (IDBBC). 932 55

This nonblinded, multicenter, randomized phase III study compares the median time to progression (primary endpoint), response rate, and quality of life, safety, and survival of docetaxel (Taxotere) vs mitomycin (Mutamycin) plus vinblastine (Velban) in patients with metastatic breast cancer in whom previous anthracycline-containing chemotherapy has failed. Patients were randomized to receive an intravenous infusion of either 100 mg/m2 of docetaxel for 1 hour every 3 weeks, or 12 mg/m2 of mitomycin every 6 weeks plus 6 mg/m2 of vinblastine every 3 weeks. This preliminary analysis presents data on 200 patients among 392 patients recruited. Median time to progression was longer in the group treated with docetaxel compared with the mitomycin/vinblastine group (17 vs 9 weeks). The overall response rates were higher with docetaxel (28% vs 13%, respectively), and fewer patients in the docetaxel group had progressive disease as their best overall response (29% vs 48%). As expected, thrombocytopenia was more common in the mitomycin/vinblastine group, and neutropenia occurred more frequently in the docetaxel group. Severe fluid retention in the docetaxel group (8.7%) resulted in treatment discontinuation in 5 patients (5%). Severe thrombocytopenia (12%) and constipation (6%) led to treatment discontinuation in 7 and 3 patients, respectively, in the mitomycin/vinblastine group. Based on this preliminary analysis, docetaxel appears to be equally as safe as and more active than mitomycin/ vinblastine in patients with metastatic breast cancer in whom previous anthracycline-containing chemotherapy has failed. These results are subject to cautious interpretation because this analysis was conducted on the first 200 patients who finished the study treatments, and these preliminary results may underestimate response and overstate treatment discontinuation rates. Thus, the final analysis on the entire patient population is necessary to confirm these preliminary findings.
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PMID:Docetaxel vs mitomycin plus vinblastine in anthracycline-resistant metastatic breast cancer. 936 38

Tremendous progress has been made in the medical treatment of advanced colorectal cancer during the past 2 to 3 years, due to the availability of several new drugs. Of these new agents, irinotecan (CPT-11 [Camptosar]) seems to be one of the most active against advanced colorectal cancer. It is, therefore, a good candidate for combination with the more classic cytotoxic agents for this disease. This article summarizes several European phase I and II studies in which irinotecan has been combined with (1) fluorouracil (5-FU) alone, given as a repeated bolus injection or a protracted infusion; (2) 5-FU modulated by folinic acid (leucovorin) according to different schedules; or (3) mitomycin (Mutamycin). All of these studies have demonstrated clinical responses in patients with advanced colorectal carcinoma, including complete responses. The toxicity profiles of the various combinations seem to be acceptable; neutropenia and delayed diarrhea are the most frequent side effects. Large phase III studies are still warranted to demonstrate the benefit of these irinotecan-based regimens.
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PMID:European experience with irinotecan plus fluorouracil/folinic acid or mitomycin. 972 94

To date, in cases of advanced or recurrent breast cancer, combination chemotherapy including anthracycline have been used for 1st-line treatment. Mitomycin C and oral 5-FU were used for cases refractory to such treatment, but the response rate was not satisfactory. Docetaxel is one of the most promising drugs to have emerged in recent years, with phase II studies in previously untreated metastatic breast cancer indicating a high overall response rate of approximately 60%, in the refractory cases for anthracyclines, indicating an overall response rate of 40% using docetaxel at 75 to 100 mg/m2 as a 1-hour intravenous infusion every 21 days. In Japan, the overall response rate was reported as about 50% using single docetaxel given at 60 mg/m2 every 21 days. The dose-limiting toxicity is myelosuppression, which is dose-but not schedule-dependent. In most published studies, there is a 90-95% incidence of grade 3 or 4 neutropenia when docetaxel is administered every 3 weeks. In recent studies, for the purpose of reducing the severity of myelosuppression, weekly docetaxel seems to be an effective and feasible treatment for advanced or recurrent breast cancer.
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PMID:[Docetaxel]. 1168 Dec 43

The purpose of this phase II study was to evaluate the clinical efficacy of mitomycin C and vinblastine in patients with anthracycline-resistant metastatic breast cancer. This single-center, non-randomized trial enrolled 39 patients. Eligible patients must have received at least three chemotherapy regimens with epirubicin or CAF and had treatment failure while on chemotherapy or within 6 months of completing therapy. Treatment consisted of mitomycin C at a starting dose of 8 mg/m2 on day 1 and vinblastine (8 mg/m2, days 1 and 28). The regimen was repeated every 6 weeks with a 20% dose escalation of both drugs after the first cycle in the absence of grade III hematologic or other toxicity. On an intent-to-treat basis, 38 patients were eligible for assessment; 9 (23.7%, 95% confidence interval 1.92-2.45%) achieved a partial response and 13 (34.2%) had stable disease. The median time to disease progression was 6.21+/-4.26 months (range, 1-15; 95% confidence interval, 4.81-7.61), and the median survival was 10.76+/-7.6 (range, 1-29; 95% confidence interval 8.0-13.1%). Responsive patients had a significantly better survival than those with stable and progressive disease. Treatment was well tolerated. Anemia and neutropenia (grade I-III) developed in 28.9% and 26.3% of the patients, respectively. One patient with grade III granulocytopenia developed fever and infection that required hospitalization. Moderate neurotoxicity, myalgia, constipation, diarrhea and alopecia were observed. No toxic death occurred. Mitomycin C plus vinblastine is an effective and well-tolerated regimen for anthracycline resistant cancer.
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PMID:Mitomycin C and vinblastine in anthracycline-resistant metastatic breast cancer: a phase II study. 1198 93


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