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)

For over four decades, 5-fluorouracil (5-FU) has been the mainstay of therapy for colorectal cancer and a major cytotoxic agent for treating gastrointestinal tumors and a variety of others, including breast and head and neck cancers. Xeloda (capecitabine) is a new drug that is administered orally and has been rationally designed to generate 5-FU selectively within solid tumors. Theoretically, it has two major advantages, which should translate into an improved therapeutic index: firstly, enhanced drug concentration at the cancer site and therefore greater anti-tumor activity and secondly, reduced drug levels in non-tumor tissues, with a consequent reduction in systemic toxicity. After promising preclinical studies, phase I clinical trials of Xeloda have been performed with a variety of schedules, both with and without the oral biomodulator leucovorin. Anti-tumor activity has been observed with all regimens tested. In the setting of colorectal cancer, a randomized phase II study substantiated the phase I reports of activity and established the most promising regimen for phase III clinical trials. Patients in the phase II trial were randomly selected to receive either continuous Xeloda, intermittent Xeloda or intermittent Xeloda plus leucovorin. There were complete or partial responses in 21% of patients in the continuous arm, 24% in the intermittent arm, and 23% in the arm with intermittent Xeloda plus leucovorin. In addition, 51-63% of patients in each arm achieved stable disease. Therapy was well tolerated in all three arms. The intermittent regimen of Xeloda alone was associated with a longer time to disease progression and offered a one-week rest period to the patient. It was therefore selected for subsequent studies. Two randomized phase III trials of Xeloda versus the 'Mayo' regimen in patients with advanced colorectal cancer have completed recruitment. They are designed to demonstrate at least equivalent efficacy, with important secondary endpoints of comparisons of toxicity, medical care utilization, and quality of life. No formal results are yet available from these studies. The same regimen of Xeloda is now being evaluated in a large scale adjuvant study, which is expected to recruit approximately 1,700 Dukes' C colonic cancer patients (X-ACT study). The modest toxicity of Xeloda (particularly its low incidence of neutropenia) makes it a suitable candidate for novel combination therapies involving other agents that are active in colorectal cancer, including camptothecin and its analogues, oxaliplatin and radiotherapy. Further studies of Xeloda can be expected with other diseases known to be responsive to fluoropyrimidines, together with diseases traditionally thought to be resistant.
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PMID:Potential of Xeloda in colorectal cancer and other solid tumors. 1043 14

Despite the long clinical history of 5-FU in gastrointestinal cancer, the development of oral agents has been a productive endeavor, and oral fluoropyrimidine agents are likely to play an important role in the management of colorectal cancer. Results of recent trials in advanced/metastatic colorectal cancer have shown equivalence of response rates, time to disease progression, and median survival and reduced rates of neutropenia and stomatitis with oral capecitabine (Xeloda) or UFT/leucovorin compared with standard fluorouracil (5-FU)/leucovorin regimens. Evaluation of these oral agents in adjuvant therapy, in combination chemotherapy, and in combination with radiation therapy is ongoing.
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PMID:Role of oral chemotherapy in colorectal cancer. 1119 16

Capecitabine (Xeloda) is an oral prodrug that is enzymatically converted to fluorouracil (5-FU) within cancer cells. Data from two large phase III trials performed in patients receiving first-line chemotherapy for metastatic colorectal cancer showed that capecitabine yielded higher objective response rates and equivalent median time to tumor progression and overall survival rates as 5-FU/leucovorin. In these studies, capecitabine demonstrated lower rates of diarrhea, stomatitis, nausea, and severe neutropenia than bolus 5-FU/leucovorin, but a higher rate of hand-foot syndrome and hyperbilirubinemia. The natural extension of this work has been to evaluate substitution of capecitabine for 5-FU/leucovorin in combination chemotherapy trials with irinotecan (CPT-11, Camptosar) or oxaliplatin (Eloxatin). This is especially important due to concerns regarding toxicities observed with regimens that combine bolus 5-FU/leucovorin with irinotecan or oxaliplatin. Phase I/II and phase II trials of capecitabine in combination with irinotecan or oxaliplatin in patients with advanced disease indicate that the combinations are well tolerated and produce response rates that are in the range of those that would be expected with infusional 5-FU/leucovorin combined with irinotecan or oxaliplatin. Phase III trials have been initiated in the advanced disease and adjuvant settings and should help determine the efficacy, toxicity, and tolerability of the capecitabine/irinotecan or capecitabine/oxaliplatin combination in direct comparison to intravenous 5-FU/leucovorin and irinotecan or oxaliplatin.
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PMID:Current status of capecitabine in the treatment of colorectal cancer. 1252 Jun 35

The combination of capecitabine (Xeloda) and oxaliplatin (Eloxatin), or XELOX, is an effective and safe approach to the treatment of advanced colorectal cancer, with the potential advantage of convenience over standard combination regimens. In a large multicenter phase II trial for patients with metastatic colorectal cancer (N = 96), first-line treatment with oral capecitabine at 1,000 mg/m2 twice daily for 14 days and oxaliplatin at 130 mg/m2 by 2-hour infusion on day 1 every 21 days produced objective response in 55% of patients and stable disease (greater than 3 months) in a further 32%. Preliminary data indicate a median progression-free survival of 7.6 months (with 14% of patients still having not progressed) and median survival of over 16 months (with 59% of patients still alive); the 1-year survival rate was 72%. Grade 3 or 4 toxicity was relatively infrequent; in particular, grade 3 hand-foot syndrome occurred in just 3% of patients and severe neutropenia in only 6%. Treatment delivery was highly successful, with a median of 10 cycles being administered (range: 1-23 cycles). Both efficacy and safety outcomes with the XELOX combination compare well with those observed with infusional fluorouracil (5-FU)/leucovorin plus oxaliplatin (FOLFOX4) in first-line treatment for advanced disease. However, 3-weekly XELOX requires less time in hospital and is simpler than the 2-weekly standard FOLFOX4 regimen. Phase III trials comparing XELOX with infusional 5-FU/leucovorin/oxaliplatin are ongoing.
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PMID:Can capecitabine replace 5-FU/leucovorin in combination with oxaliplatin for the treatment of advanced colorectal cancer? 1252 Jun 36

The effectiveness and tolerability of xeloda (capecitabine), a tumor-reactivated oral fluoropyrimidine, alone were investigated in 19 patients, aged 39-79, with relapsing and cisplatin-resistant ovarian tumors. Unfavorable prognosis of chemotherapy was in 11 cases (57.8%): cisplatin-resistant tumors (7) and early relapse--before month 6 (4). Xeloda was administered orally, 1,250 mg/m2, twice a day, for two weeks at an interval of one week. A total of 68 cycles (an average of 3.6 cycles) were evaluated. Complete response was registered in 1, partial--4, and stabilization--4 cases. Total response was in 26.3%, clinically significant effect--47.3% (9 out of 19). Toxic side-effects generally persisted with in stage I-II (palm-and-sole syndrome, leukopenia, neutropenia, sickness, vomiting, diarrhea) without interfering with the treatment.
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PMID:[Experience with xeloda (capecitabine) as a component of chemotherapy for relapsing cisplatin-resistant ovarian tumors]. 1278 4

The combination of cisplatin and 5-fluorouracil (5-FU) is considered to be the standard treatment in induction chemotherapy for patients with squamous cell carcinoma of the head and neck. Capecitabine (Xeloda) is an oral fluoropyrimidine that is preferentially activated at the tumoral level, exploiting the higher thymidine phosphorylase activity in tumoral tissue. This phase I trial was conducted in patients with locally recurrent or metastatic head and neck carcinoma. The treatment plan included cisplatin on day 1 every 21 days, followed by capecitabine twice daily from day 2 to day 15, with a 1-week rest period. Pharmacokinetic investigations concerned plasma measurement of unchanged capecitabine, 5'-deoxy-5-fluorocytidine, 5'-doxifluridine and 5-FU using an optimized high performance liquid chromatography method, and cisplatin measurement in plasma using a limited sampling procedure. Twenty-one patients were included (mean age 61 years, range 46-76 years). Dose (mg/m(2)) increments for cisplatin and capecitabine (b.i.d.), respectively, were as follows: level 1, 80 and 1000 (three patients); level 2, 100 and 1000 (12 patients); and level 3, 100 and 1125 (five patients). Dose-limiting toxicities occurring during the first cycle (grade >/= 3) were observed on level 2 (one patient with diarrhea, nausea, vomiting, hand-foot syndrome, one toxic death due to renal failure and neutropenia, one patient with neutropenia) and on level 3 (one patient with diarrhea, one patient with hand-foot syndrome and one patient with neutrothrombocytopenia). Due to delayed side-effects, 14 patients (67%) had repeated cycles every 28 days instead of 21 days as initially planned. Objective response was obtained in seven patients (three complete responses and four partial responses). There was no evidence of pharmacokinetic-pharmacodynamic relationships with the drugs and metabolites investigated. Combination of capecitabine and cisplatin is feasible, with a very promising response rate. The recommended doses for further phase II studies are those of level 2 with cisplatin 100 mg/m(2) on day 1 and capecitabine 1000 mg/m(2) b.i.d. on days 1-14, every 28 days.
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PMID:Phase I and pharmacokinetic study of the association of capecitabine-cisplatin in head and neck cancer patients. 1450 61

As capecitabine (Xeloda) is converted to 5-FU within tumours it can produce 5-FU-like side effects. However, diarrhoea, stomatitis, nausea, alopecia and neutropenia are significantly less frequent than with i.v. 5-FU. Hand-foot syndrome (HFS) is the only clinical adverse event occurring more often during capecitabine treatment. These findings in MCRC have also been confirmed in a large phase III trial in early stage colon cancer (X-Act adjuvant study) and phase II clinical trials in metastatic breast cancer. Because capecitabine is taken in the outpatient setting, the nurse and/or supervising clinician are responsible for educating patients how to use it correctly and on the nature/recognition/severity of adverse events. Patients need to be aware that temporary interruptions/dose modifications do not reduce the overall efficacy of capecitabine and will most likely lead to a resolution of side effects. Consequently, oncology nurses will be assuming a more significant and pivotal role in the efficient education and support of patients during home-based therapy with capecitabine.
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PMID:Management of adverse events and other practical considerations in patients receiving capecitabine (Xeloda). 1534 79

This report here is the case of a 52-year-old male patient who suffered from extremely severe haematological toxicities (G4 neutropenia, G4 thrombocytopenia) while undergoing Xelox (Xeloda + Oxaliplatin) treatment for his multifocal hepatocarcinoma. Despite appropriate supportive treatment, his condition quickly deteriorated and led to death. It was hypothesized that dihydropyrimidine deshydrogenase (DPD) gene polymorphism could be, at least in part, responsible for this fatal outcome. To test this hypothesis, both phenotypic and genotypic studies were undertaken, and fully confirmed the DPD-deficient status of this patient. Uracil to dihydrouracil ratio in plasma was evaluated as a surrogate marker for DPD deficiency, and showed values out of the range previously recorded from a reference, non-toxic population. Interestingly, the canonical IVS14+1G>A single nucleotide polymorphism, usually associated with the most severe toxicities reported with 5-fluorouracil (5-FU), was not found in this patient, but further investigations showed instead a heterozygosity for the 1896C>T mutation located in the exon 14 of the DPYD gene. Taken together, the data strongly suggest for the first time that a toxic-death case after capecitabine-containing protocol could be, at least in part, linked with a DPD-deficiency syndrome. The case reported here warrants therefore systematic detection of patients at risk, including when oral capecitabine is scheduled.
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PMID:Toxic death-case after capecitabine + oxaliplatin (XELOX) administration: probable implication of dihydropyrimidine deshydrogenase deficiency. 1629 36

We evaluated the safety and efficacy of primary systemic chemotherapy (PSC) with docetaxel (DOC), epirubicin (EPI) and capecitabine (Xeloda:XLD) in 10 patients with advanced breast cancer. Their mean age was 54.7 years,and preoperative stages were IIB, seven cases; IIIA, two; and IV, one,respectively. The regimen consisted of XLD (2,400 or 3,000 mg/day) orally for 14 consecutive days, and DOC (60 or 70 mg/m2) and EPI (50 or 60 mg/m2) intravenously on day 8. This was repeated 4 times every 3 weeks. One patient discontinued this regimen after one course at her own request. Although the results revealed leucopenia and neutropenia of more than grade 3 in 8 and 10 patients,they could be treated on an outpatient basis with the use of G-CSF to maintain this regimen. Alopecia of grade 2 was found in all patients,neutropenic fever of more than 38.5 degrees C in 5,and hand-foot syndrome in 3. Downstaging after PSC was demonstrated in 7 cases (Stage IIB to I, three cases; IIB to IIA, three; and III A to I, one), with a response rate of 77.8%. Breast conserving therapy was performed in 8/10 patients. Pathological findings on cytological degeneration showed grade 0, one; grade 1a,seven; grade 2, one; and grade 3, one, respectively. Axillary lymph node metastasis was revealed in 7 cases. This regimen would be an alternative to PSC on an outpatient basis while taking great care of myelosuppression and hand-foot syndrome.
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PMID:[Pilot study of primary systemic chemotherapy with docetaxel (DOC), epirubicin (EPI) and capecitabine (Xeloda) in patients with advanced breast cancer]. 1641 Jun 96

Colorectal cancer continues to pose a major public health threat in the United States. Without postsurgical adjuvant therapy, approximately 50% of patients will have recurrent disease and die within five years. Since 1990, five new chemotherapy agents have been added to the therapeutic armamentarium for management of colorectal cancer, and agents traditionally used to treat metastatic and advanced disease increasingly are being applied in the adjuvant setting. One such treatment, capecitabine, offers patients the benefit of oral dosing and permits at-home self-management. A phase III randomized trial, Xeloda in Adjuvant Colorectal Cancer Treatment, demonstrated that treatment with single-agent capecitabine was equivalent to bolus 5-fluorouracil with leucovorin with respect to disease-free survival and overall survival, with significantly less diarrhea, stomatitis, neutropenia, nausea and vomiting, and alopecia. This article reviews the findings and discusses how oncology nurses can help provide effective education and monitoring for patients using oral treatment in the adjuvant setting.
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PMID:Capecitabine: a new adjuvant option for colorectal cancer. 1692 1


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