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Biomedical subjects

G M Higa

Publications and source records attributed to G M Higa.

18 recordsLinked to original sources
PubMed2001

Aromatase inhibitors for breast cancer: pharmacoeconomic considerations.

Although the anti-oestrogen tamoxifen is recognised as the treatment of choice for both premenopausal and postmenopausal women with advanced hormone-dependent breast cancer, oestrogen deprivation can also be achieved, with apparently less adverse-effects, through selective inhibition of aromatase. Recent clinical trials have demonstrated the efficacy and tolerability of the new generation of aromatase inhibitors as second-line and first-line therapy in postmenopausal women with breast cancers who were eligible for endocrine treatment. Speculating that administration of aromatase inhibitors will not be limited to postmenopausal breast cancer, a pharmacoeconomic perspective is considered based on available data and putative therapeutic application during various phases of the disease.

Antineoplastic Agents, Hormonal↗
PubMed2000

Altering the estrogenic milieu of breast cancer with a focus on the new aromatase inhibitors.

Aromatase is a dual-enzyme complex that catalyzes the synthesis of estrogen from androgenic precursors. Although evidence implicates estrogens in the pathogenesis of breast cancer, recent findings suggest that deregulation of aromatase may be a crucial link between these hormones and this neoplasm. Whereas tamoxifen is the endocrine therapy of choice, selective inhibition of aromatase may be equally effective, and possibly less toxic, in the management of patients with hormone-responsive breast tumors.

Aromatase↗
PubMed2000

New generation aromatase inhibitors in breast cancer. Weighing out potential costs and benefits.

Endocrine therapy is the oldest and still one of the most effective forms of systemic therapy for breast cancer. Unfortunately, only one-third of all breast carcinomas respond to a strategy that modifies the activity of estrogen at the level of the tumour. Therefore, it is important that patients with cancer likely to respond are reliably identified. Substantial evidence indicates that tumour estrogen receptor level is the best predictor of response to hormonal therapy. Although antiestrogen therapy is still considered the endocrine modality of choice for all stages of breast cancer, there is renewed interest in finding new agents with improved therapeutic indices. The development of agents which selectively suppress aromatase, a key enzyme in estrogen biosynthesis, can be attributed not only to the importance of extraglandular aromatase activity, but also to the unparalleled success of tamoxifen. The present status, emerging roles and concerns of the new aromatase inhibitors are discussed in order to assess their potential costs and therapeutic merit.

Antineoplastic Agents↗
PubMed1999

Pharmacodynamic profile of prolonged etoposide administration in patients with small cell lung cancer and non-Hodgkin's lymphoma.

STUDY OBJECTIVE: To determine whether therapeutic drug monitoring can enhance administration of etoposide in patients with drug-responsive neoplasms. DESIGN: Prospective, open-label study. SETTING: University-affiliated hospital and cancer center. PATIENTS: Sixteen patients with small cell lung cancer or low-grade non-Hodgkin's lymphoma. INTERVENTIONS: Patients were treated with etoposide, 25 mg/m2/day over 24 hours by continuous infusion for 35 days. Peripheral blood samples were collected twice a week to measure etoposide levels. Plasma was separated, frozen and stored at -20 degrees C until assayed. MEASUREMENTS AND MAIN RESULTS: Steady-state plasma etoposide concentrations (ECpss) were determined and used to calculate total systemic clearance (Clsys). Despite differences in dosage and administration schedules, etoposide Clsys was similar to previous reports. In addition, a biexponential relationship between ECpss and absolute neutrophil count was demonstrated by nonlinear least squares estimation. Values generated from this equation indicated that ECpss above 1.5 microg/ml was strongly associated with grade III-IV leukocyte toxicity. Although less precise, there may also be a correlation between ECpss and antitumor activity. CONCLUSION: Based on these findings, we propose a pharmacodynamic construct that uses measurements of both pharmacokinetic (ECpss, Clsys) and pharmacodynamic (hematologic toxicity, tumor response) parameters for patients with etoposide-sensitive tumors. Therapeutic drug monitoring may be able to mitigate hematologic toxicity.

Adult↗
PubMed1998

Anastrozole: a selective aromatase inhibitor for the treatment of breast cancer.

The role of anastrozole, a new selective aromatase inhibitor, in treating hormone-responsive metastatic breast cancer is discussed. Treatment options for hormone-dependent breast cancer focus on interfering with the endocrine system in an attempt to modify the effects of estrogen. Tamoxifen is the drug of choice for primary endocrine therapy, but there is a need for agents with similar or greater efficacy and better tolerability. Anastrozole inhibits the conversion of androgens to estrogens by aromatase. Bioavailability studies have demonstrated almost complete absorption of anastrozole after oral administration. The drug's terminal half-life after multiple doses is 50 hours. Anastrozole is cleared principally by the liver. Clinical trials comparing anastrozole with megestrol acetate demonstrated no significant differences in clinical efficacy, although a follow-up study revealed a longer median overall survival rate in patients receiving anastrozole. The drug is well tolerated. Among the most frequently reported adverse effects are asthenia, hot flashes, headache, and back pain. The recommended dosage is 1 mg daily. The average wholesale cost of month's supply of anastrozole is $187.20, compared with approximately $100 for generic megestrol acetate or aminoglutethimide plus hydrocortisone. Although anastrozole will likely become the preferred second-line agent in the treatment of postmenopausal breast cancer in patients with disease progression after tamoxifen therapy, it is not a therapeutic alternative to aminoglutethimide on the basis of approved indications. Anastrozole and other aromatase inhibitors may have multiple applications in treating hormone-responsive breast cancer.

Anastrozole↗
PubMed1998

Doxorubicin dosage guidelines in a patient with hyperbilirubinemia of Gilbert's syndrome.

OBJECTIVE: To reconcile dosage modification guidelines for doxorubicin in a patient with hyperbilirubinemia of Gilbert's syndrome (GS). CASE SUMMARY: A 62-year-old white man with concurrent diagnoses of large-cell non-Hodgkin's lymphoma and GS was treated with standard doses of a doxorubicin-containing chemotherapy regimen. No increase of end-organ toxicity was observed during four treatment cycles. DISCUSSION: The relative prevalence of GS coupled with the rising incidence of non-Hodgkin's lymphoma increases the probability that both disorders will be present in the same individual. A MEDLINE search (1966 through July 1997) revealed little, and often conflicting, information pertaining to drug metabolism and disposition in GS. In addition, no information has been reported regarding the metabolic fate of doxorubicin in these patients. It is important to emphasize that the lack of enhanced extramedullary toxicity in this patient is not conclusive evidence that the hepatic abnormality of GS had no effect on doxorubicin metabolism. CONCLUSIONS: Based on information regarding mechanisms for hepatic clearance, dosage modification of doxorubicin may not be necessary in hyperbilirubinemia of GS.

Antineoplastic Agents↗
PubMed1995

Severe, disabling neurologic toxicity following cisplatin retreatment.

OBJECTIVE: To describe a severe neurotoxic reaction following the second cycle of cisplatin-based chemotherapy. CASE SUMMARY: A patient with unresectable non-small-cell lung cancer was treated with combined chemotherapy and radiotherapy. Thirty-six hours after the second course of chemotherapy, the patient developed severe mental status changes consisting of aphasia, confusion, and agitation. Complete neurologic workup was most consistent with an acute vascular event. DISCUSSION: Reports of acute cisplatin-induced neurologic toxicity involving the central nervous system are rare. Potential risk factors are described. Mechanisms of chemotherapy-induced vascular damage are discussed. CONCLUSIONS: Total dosage and administration schedule of cisplatin are associated with an increased incidence of neuropathy. However, factors predicting the development of early, acute neurotoxicity are limited by the rarity of these events. It is probable that acute neurotoxic reactions in cancer patients are caused by an unknown complex of interactions involving drugs, tumor, and host factors.

Adenocarcinoma↗
PubMed1993

The chemohormonal therapy of metastatic melanoma: possible benefit of tamoxifen.

Metastatic melanoma is difficult to treat because of low response rates to most chemotherapy regimens and short remission durations. Recently, a new chemohormonal regimen containing BCNU, cisplatin, DTIC and tamoxifen (BCDT) has been reported to be more promising. We have treated eight patients with this regimen and five patients responded, including three with complete responses (CR). One of these patients remains in CR beyond two years. Others have also reported response rates of 50% with this regimen with a few long-term remissions also. Two of our patients developed deep venous thromboses (DVT). The increased incidence of DVT with BCDT is attributed to the tamoxifen, which nevertheless appears to be a necessary component of this regimen. In two of our patients, short courses of tamoxifen were used and they both obtained responses (one CR, one PR) without DVT. The possibility of using short-course tamoxifen to reduce the incidence of DVT in this regimen, without impairing its efficacy, should be investigated.

Adult↗
PubMed1991

The use of prophylactic eye drops during high-dose cytosine arabinoside therapy.

An ocular toxic reaction presenting as conjunctivitis or keratitis develops in a significant number of patients who are treated with high-dose cytosine arabinoside (ara-C). Although eye drops containing glucocorticoid reportedly decrease the incidence, they do not totally eliminate this side effect. In comparing this technique with artificial tears, both were found to be equally effective. The primary mechanism by which eye drops decrease ocular toxic reactions associated with high-dose ara-C is presumably due to dilution of intraocular concentrations of ara-C.

Adult↗
PubMedDate not supplied

Scientific publications and scientific style.

The publication of scientific information should be the natural outcome of research. However, scientific style demands logic, precision, clarity and brevity--qualities often setting it apart from literary style. This paper highlights a 10-step approach to preparing a scientific manuscript.

Humans↗
PubMedDate not supplied

Elevation of the erythrocyte sedimentation rate precedes exacerbation of bleomycin-induced pulmonary toxicity: report of two cases and review of literature.

Bleomycin is included in a number of potentially curative chemotherapy regimens. It is associated with distinct forms of pulmonary toxicity, with interstitial pneumonitis the most common. Early detection of pulmonary toxicity is not always predictable by monitoring serial chest radiographs and pulmonary function tests. Even newer serum markers are not useful indicators of bleomycin-induced pulmonary damage. Two patients developed bleomycin pulmonary toxicity, in both of whom increases in erythrocyte sedimentation rate (ESR) preceded clinical deterioration and radiographic changes. The ESR may have potential significance as a monitoring test in patients receiving bleomycin.

Adult↗
PubMedDate not supplied

Biological and clinical correlates after chemotherapy and granulocyte colony-stimulating factor administration.

STUDY OBJECTIVE: To evaluate specific biological markers to improve understanding and use of granulocyte colony-stimulating factor (G-CSF) in patients receiving chemotherapy DESIGN: Prospective, randomized study. SETTING: University-affiliated hospital and cancer center. PATIENTS: Twenty-five patients randomized to begin G-CSF either 24 hours after chemotherapy (standard arm), or on the day the absolute neutrophil count (ANC) was below 1000/mm3 after chemotherapy (delayed arm). INTERVENTIONS: To determine the effect of G-CSF on granulopoiesis, peripheral blood mononuclear cells were assayed by semisolid culture medium and flow cytometry for granulocyte progenitors and clonogenic CD34 antigen-positive cells. These biological markers were correlated with G-CSF administration schedules and the ANC. MEASUREMENTS AND MAIN RESULTS: The effect of timing of G-CSF administration on rate of neutrophil recovery, duration of neutropenia, length of G-CSF therapy, delays of chemotherapy cycles, and neutropenic fever events was evaluated. Regardless of G-CSF schedule or chemotherapy regimen, the appearance of mobilized hematopoietic progenitors begins at the neutrophil nadir and parallels granulocyte recovery. Our data also demonstrate that proper timing of G-CSF administration produces similar rates of neutrophil recovery and comparable clinical outcomes. CONCLUSION: Based on the correlation between biological markers and ANC, we propose that the postchemotherapy ANC is a surrogate marker of renewed granulopoietic activity. The relevance of this finding in relationship to the clinical application of G-CSF remains to be further defined.

Adult↗
PubMedDate not supplied

Acute effects of prechemotherapy filgrastim administration on late hematopoietic progenitor cells.

Administration of filgrastim influences the proliferative kinetics of myeloid progenitor cells. Even after it is discontinued, increased levels of cycling of granulocyte precursors are sustained for approximately 4 days. Beginning chemotherapy during this period of enhanced marrow activity can cause great damage to late, and possibly early, progenitor cell pools. Peripheral blood samples were collected from two research study patients who were prospectively randomized to receive filgrastim by different schedules after chemotherapy. The mononuclear cell fraction was analyzed by clonogenic progenitor cell assay and flow cytometry. Ex vivo and clinical findings were correlated with filgrastim and chemotherapy administration times. Although quantitative recovery of circulating neutrophils occurred, a substantial decrease in peripheral blood progenitor cells was observed when chemotherapy was started 72 hours after cessation of filgrastim therapy. Neutrophil recovery alone is not a precise index of short-term marrow granulocyte progenitor status. Starting chemotherapy within 72 hours of filgrastim therapy is biologically, and possibly, clinically relevant.

Adult↗