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cscdragon

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[交流] 提供两例化疗病例分析，很有启发性。

提供两例化疗病例分析，很有启发性。
FT is a 45-year-old postmenopausal woman with newly diagnosed metastatic breast cancer to the lungs and liver. She has a history of right breast cancer diagnosed three years ago [T2N1M0, ER/PR (estrogen receptor/progesterone receptor) negative and HER2-negative by FISH (fluorescent in situ hybridization)]. The cancer was treated with lumpectomy and axillary lymph node dissection followed by adjuvant chemotherapy with AC (doxorubicin plus cyclophosphamide) x four cycles followed by paclitaxel every three weeks x four cycles followed by radiation therapy to the breast and local lymphatics. She now presents with bilateral parenchymal lung and liver metastases. She is completely asymptomatic, with the exception of slight fatigue. Her laboratory parameters are within normal limits, with the exception of her breast cancer tumor marker (CA 2729), which is elevated. She is otherwise healthy with no other comorbid conditions.
Therapy for this woman would now be focused on prolonging survival and maintaining quality of life, since she is asymptomatic. Endocrine therapy is not an option for this patient due to the lack of hormone receptors on her primary tumor. Trastuzumab therapy is also not an option for this patient due to the lack of HER2 overexpression on her primary tumor. Therefore, chemotherapy would be the only option for FT at this time. She has no symptoms related to her disease at this time. There really is not a single “standard of care” for this patient. Many treatment options would be appropriate, including participation in a clinical trial. In this setting, the choice of single-agent chemotherapy is preferred and a taxane could be chosen. The new albumin-bound paclitaxel (Abraxane) would be an appropriate choice, either as an every three-week infusion or as a weekly infusion. Given the data supporting paclitaxel’s superiority and tolerability when given weekly, this would be preferred for the albumin-bound paclitaxel as well. Other new chemotherapies may soon be available as well, and participation in a clinical trial may benefit her and/or future patients in the development of these agents.

病例1 一45 岁绝经后妇女，最近诊断为肺、肝脏转移性乳腺癌。3 年前她诊断为右乳腺癌（T2N1M0,ER-/PR-,FISH法HER2-），当时行肿块切除和腋窝淋巴结清扫术，接着行辅助化疗：AC 方案（阿霉素+环磷酰胺）4 周期→泰素（每3 周一次）4 周期，接着行乳腺及局部淋巴结放疗。现在她两侧肺和肝脏有转移灶。除有轻微疲乏外，她无其它症状。实验室检查除CA2729升高外，其余指标均在正常范围。她没有并发其它疾病。
对这个病人的治疗应着重于延长生存期和维持生存质量，因为她没有症状。由于她的肿瘤缺乏激素受体，因此不宜选择内分泌疗法，又由于HER2 缺乏表达，因此亦不宜选择曲妥株单抗。化疗是她唯一的选择。没有一个单纯的标准的化疗方法，有许多方法可供她选择，包栝参加临床试验。对这个病例，单药化疗应优先采用，紫衫醇类药物可供选择。Abraxane是一种新的紫衫醇类药物，为与白蛋白结合的泰素，合适该病人使用，可每3 周一次静脉用药，亦可每周一次用药。因资料表明每周给药的优势性和耐受性，Abraxane亦可适于每周一次用药。其它新的化疗药物不久将出现，在新药开发过程中，参加临床试验可能对这个患者和/或将来的病人有益。
KP is a 52-year-old postmenopausal woman with newly diagnosed metastatic breast cancer to the lungs. She has a history of left breast cancer, which was treated 14 months ago with a modified radical mastectomy with axillary lymph node dissection followed by adjuvant chemotherapy with AC (doxorubicin plus cyclophosphamide) x four cycles followed by paclitaxel x four cycles. She now presents with new-onset shortness of breath and a dry cough. A chest x-ray reveals suspicious nodules in both lungs and a CT scan of the chest confirms that these nodules are suspicious for metastatic breast cancer. Since she is a heavy smoker, a biopsy of one of these lesions is done to rule out primary lung cancer. The biopsy reveals metastatic adenocarcinoma consistent with a breast primary origin (ER/PR negative and HER2 positive by FISH). She has had a history of multiple bronchial infections but is otherwise healthy. Her laboratory parameters are within normal limits.
For this patient, endocrine therapy is not an option due to the lack of hormone receptors on her lung metastases. She would be a candidate for trastuzumab-based therapy due to the HER2 positivity of her tumor. Trastuzumab can be given as a single agent, but combining it with chemotherapy has been shown to be superior to chemotherapy alone, and the clinical benefit seen with the combination is improved compared to single-agent trastuzumab. However, combination chemotherapy plus trastuzumab also has more toxicity related to its administration. These risks and benefits should be weighed carefully for each individual patient when making treatment decisions of this nature. If the patient decides to take combination chemotherapy plus trastuzumab, the use of concurrent anthracyclines with trastuzumab is currently contraindicated. There are a number of clinical trials ongoing that are investigating how to safely incorporate an anthracycline into a trastuzumab regimen. Therefore, the patient would be able to consider such a trial if one were available in her local area. Paclitaxel and docetaxel plus trastuzumab have been shown to improve survival compared to chemotherapy alone. These options would be available to this patient outside the context of a clinical trial. Due to the relatively close proximity to the adjuvant taxane she recently received (one month ago), this approach may or may not provide benefit for this patient at this time. A combination of trastuzumab with either navelbine or gemcitabine or possibly capecitabine may provide benefit for this patient. Due to antagonistic effects demonstrated in animal models, the combination of capecitabine and trastuzumab is very controversial

病例2 女性，52 岁，绝经后。最近诊断为肺转移性乳腺癌。14 个月前她诊断为左乳腺癌，当时行修正根治性乳腺切除术和腋窝淋巴结清扫术，接着行辅助化疗：AC 方案（阿霉素+环磷酰胺）4 周期→泰素4 周期。现在她感觉气短和干咳，胸片显示两肺可疑小结节，CT 扫描进一步证实为可疑肺转移性乳腺癌。由于她嗜烟，因此取其中一个结节做活检以排除原发性肺癌。或检显示转移性乳腺癌，与原发乳腺癌一致（ER-/PR-,FISH法HER2 +）。曾有多次支气管感炎史，其余均健康。实验室指标均在正常范围。
该病人肺部转移灶缺乏激素受体，因此不宜选择内分泌疗法。由于HER2 +，她合适选用含曲妥株单抗的疗法。曲妥株单抗可单独给药，但联合化疗临床疗效优于单独给药，然而联合化疗亦增加了曲妥株单抗的毒性。因此，风险与疗效须仔细权衡。假如该病人决定采用化疗+曲妥株单抗，须注意，同时应用蒽环类抗生素和曲妥株单抗在目前是禁忌的。有许多临床试验在研究如何安全地将蒽环类抗生素结合到含曲妥株单抗的方案中。若该病人所在地有这样的临床试验，可考虑参加。紫衫醇或多西紫衫醇+曲妥株单抗较单用化疗可提高生存率。在没有上述临床试验的情况下可选择紫衫醇或多西紫衫醇+曲妥株单抗这些方法。然而，由于她刚刚接受过紫衫醇辅助治疗（1 个月前），因此再用紫衫醇或多西紫衫醇对现在该病人可能有益，亦可能无益。曲妥株单抗联合诺维本或吉西他滨对该病人可能有益。由于动物模型显示曲妥株单抗与卡培他滨呈拮抗作用，因此曲妥株单抗联合卡培他滨在临床上存在争议。

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