Pharmacogenetics as a Predictor of Toxicity in Pre-Menopausal Women Receiving Doxorubicin and Cyclophosphamide in Early Breast Cancer
A Pilot Study of Cytochrome P450 Pharmacogenetics as a Predictor of Toxicity in Pre-Menopausal Women Receiving Doxorubicin and Cyclophosphamide in Early Breast Cancer
The goal of this pilot study is to delineate the role of genetic variations in premature menopause, hot flashes, and other toxicities in a cohort of premenopausal women with early breast cancer.
Primary Objective- To ascertain the effect of common variant alleles of CYP450 2B6, 2C19, 2C9, and 3A5 in pre-menopausal women with breast cancer receiving anthracycline and cyclophosphamide based chemotherapy as it relates to occurrence of premature menopause (defined as more than 12 months of amenorrhea and serum estradiol and FSH levels consistent with post-menopausal status)
Secondary Objective #1- To obtain pilot data on the effect of common variant alleles of CYP450 2B6, 2C19, 2C9, and 3A5 in pre-menopausal women with breast cancer receiving anthracycline and cyclophosphamide based chemotherapy as it relates to occurrence of hot flash frequency, and other common toxicities of therapy requiring dose delay or reduction.
Secondary Objective #2- To obtain pilot data on the correlation of hot flashes with serum levels of serotonin, tryptophan, and their metabolites and with polymorphisms of the serotonin transporter and receptor genes.
調査の概要
状態
条件
詳細な説明
There is a clear survival benefit with the use of adjuvant cytotoxic therapy for most women with invasive breast cancer, even in those who have hormone receptor positive disease and receive adjuvant hormonal therapy with tamoxifen.1 In addition, several trials have shown a benefit for anthracycline based regimens over the more classic combination of cyclophosphamide, methotrexate, and 5-fluorouracil.1-4 The improved efficacy with taxanes in the adjuvant setting has more recently been demonstrated for patients with lymph-node positive disease.5-8 Despite clear survival benefits with cytotoxic therapy, the 10 year-disease specific mortality remains suboptimal at 69-78% and 49-53% for patients with and without lymph node involvement, respectively.9
Of the 180,000 women diagnosed with breast cancer in the United States, about one-fourth are pre-menopausal.10-13 Breast cancer clearly represents one of the most commonly diagnosed malignancies in this patient population. With the common use of adjuvant chemotherapy, long-term sequelae of treatment are becoming increasingly important. In addition to the acute toxicities of anthracycline and cyclophosphamide-based regimens,5 one side effect with both psycho-social and physical implications is pre-mature menopause.13-17 The frequency of menopause induced by poly-agent chemotherapy ranges from 34-89%.16,18,19 Multiple factors (both patient and drug-related) play a role in explaining this large variability. The age of the patient (at time of therapy),13,19,20 type of chemotherapy drugs,18,21 and duration and intensity22 of therapy all influence the overall likelihood of a patient prematurely entering menopause after therapy. In a previously reported study, age and systemic therapy were important variables in determining menopause in women with loco-regional breast cancer in multivariate analysis.19 Women with advancing age had a higher rate of menopause as expected. Hormonal therapy, and to a much greater degree, systemic therapy predicted early menopause. The combination of systemic and hormonal therapy appeared to have an additive effect on induction of menopause. Of importance, however, the added impact of hormonal therapy (when added to cytotoxic therapy) appears to play a minimal role in the induction of menopause when compared to cytotoxic therapy alone. It is also likely that intrinsic host genetic variability may also play a role as well. The variable ability to metabolize and clear a drug may, in part, affect efficacy and toxicity of these drugs and may ultimately impact the effect of the drug on ovarian function. One important example of this relates to polymorphisms in enzymes important in the clearance of the described drugs. To date, little work has been done to understand the importance of inter-individual, host specific variability on the risk of a breast cancer patient experiencing drug-induced, pre-mature menopause.
研究の種類
入学 (実際)
連絡先と場所
研究場所
-
-
Indiana
-
Indianapolis、Indiana、アメリカ、46202
- Indiana University Cancer Center
-
-
参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
サンプリング方法
調査対象母集団
説明
Inclusion Criteria:
- Histologically or cytologically confirmed adenocarcinoma of the breast and appropriate for treatment with Doxorubicin and Cyclophosphamide.
- Age > 18 years and <45 years.
- ECOG performance status of 0 to 2.
- Signed informed consent.
- Premenopausal: defined as regularly occurring menstrual cycles or serologic estradiol and FSH levels consistent with premenopausal status.
Exclusion Criteria:
- Patients with distant metastatic disease will be excluded.
- Pregnancy or breast feeding (women of childbearing potential must have a negative pregnancy test). Women of childbearing potential must be willing to consent to using effective contraception (oral contraceptive pill or implant or barrier method) while on treatment and for a 30 days after taking the last dose of chemotherapy.
- Male sex will be excluded.
- Use of agent designed to suppress ovarian function (i.e. LHRH agonist).
- Use of exogenous estrogen (hormone replacement therapy) will be prohibited with the exception of topical vaginal preparations (as deemed necessary by the treating physician) and oral contraceptives.
研究計画
研究はどのように設計されていますか?
デザインの詳細
協力者と研究者
捜査官
- 主任研究者:Bryan Schneider, MD、Indiana University
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
この情報は、Web サイト clinicaltrials.gov から変更なしで直接取得したものです。研究の詳細を変更、削除、または更新するリクエストがある場合は、register@clinicaltrials.gov。 までご連絡ください。 clinicaltrials.gov に変更が加えられるとすぐに、ウェブサイトでも自動的に更新されます。
乳がんの臨床試験
-
Tianjin Medical University Cancer Institute and...Guangxi Medical University; Sun Yat-sen University; Chinese PLA General Hospital; The First Affiliated... と他の協力者完了
-
Jonsson Comprehensive Cancer CenterNational Cancer Institute (NCI); Highlight Therapeutics積極的、募集していない平滑筋肉腫 | 悪性末梢神経鞘腫瘍 | 滑膜肉腫 | 未分化多形肉腫 | 骨の未分化高悪性度多形肉腫 | 粘液線維肉腫 | II期の体幹および四肢の軟部肉腫 AJCC v8 | III期の体幹および四肢の軟部肉腫 AJCC v8 | IIIA 期の体幹および四肢の軟部肉腫 AJCC v8 | IIIB 期の体幹および四肢の軟部肉腫 AJCC v8 | 切除可能な軟部肉腫 | 多形性横紋筋肉腫 | 切除可能な脱分化型脂肪肉腫 | 切除可能な未分化多形肉腫 | 軟部組織線維肉腫 | 紡錘細胞肉腫 | ステージ I 後腹膜肉腫 AJCC (American Joint Committee on Cancer) v8 | 体幹および四肢の I 期軟部肉腫 AJCC v8 | ステージ... およびその他の条件アメリカ