Vuky Jacqueline, Porter Christopher, Isacson Christina, Vaughan Matthew, Kozlowski Paul, Picozzi Vincent, Corman John
Section of Hematology/Oncology, Virginia Mason Medical Center, Seattle, Washington 98101, USA.
Cancer. 2009 Feb 15;115(4):784-91. doi: 10.1002/cncr.24092.
Prostate cancer trials investigating neoadjuvant hormonal therapy, followed by surgery, have demonstrated that elimination of all tumor cells from the primary site is rare. The authors report a phase 2 trial assessing the efficacy and toxicity of docetaxel and gefitinib in patients with high-risk localized prostate cancer as neoadjuvant therapy before radical prostatectomy (RP).
Thirty-one patients with high-risk prostate cancer were treated with docetaxel and gefitinib for 2 months before RP. All patients met the criteria of clinical stage T2b-3 or serum prostate-specific antigen (PSA) level >20 ng/mL, or Gleason score of 8 to 10. The primary endpoint was pathologic complete response. Secondary objectives included clinical response. When available, endorectal coil magnetic resonance imaging (eMRI) was performed as part of clinical response evaluation. Immunohistochemical staining of epidermal growth factor receptor and HER-2/neu was performed on prechemotherapy and postchemotherapy prostate tissue.
The median age of the patients was 60 years, the median pretreatment PSA level was 7.43 ng/mL, and the median Gleason score was 8. Clinical staging prior to treatment consisted of: T1 in 4 patients, T2 in 17 patients, and T3 in 10 patients. One patient with enlarged pelvic adenopathy and T4 disease did not undergo RP. Thirty patients received all scheduled therapies including RP. Grade 3 toxicities included asymptomatic liver function test elevation in 4 (13%) patients, diarrhea in 1 (3%) patient, and fatigue in 1 (3%) patient. One patient experienced grade 4 toxicity with elevated alanine aminotransferase. RP specimen pathology demonstrated residual carcinoma in all cases. Twenty-nine (94%) patients achieved a clinical partial response, including 35% of patients who demonstrated radiographic improvement on eMRI.
No pathologic complete response was noted in 31 patients treated with docetaxel and gefitinib. This combination was well tolerated, and did not result in increased surgical morbidity.
研究新辅助激素治疗后再行手术的前列腺癌试验表明，从原发部位清除所有肿瘤细胞的情况很少见。作者报告了一项2期试验，评估多西他赛和吉非替尼作为高危局限性前列腺癌患者根治性前列腺切除术（RP）前新辅助治疗的疗效和毒性。
31例高危前列腺癌患者在RP前接受多西他赛和吉非替尼治疗2个月。所有患者均符合临床分期T2b - 3或血清前列腺特异性抗原（PSA）水平>20 ng/mL，或Gleason评分8至10的标准。主要终点是病理完全缓解。次要目标包括临床反应。如有条件，进行直肠内线圈磁共振成像（eMRI）作为临床反应评估的一部分。对化疗前和化疗后的前列腺组织进行表皮生长因子受体和HER-2/neu的免疫组织化学染色。
患者的中位年龄为60岁，治疗前PSA水平中位数为7.43 ng/mL，Gleason评分中位数为8。治疗前的临床分期包括：4例T1期，17例T2期，10例T3期。1例盆腔淋巴结肿大且为T4期疾病的患者未接受RP。30例患者接受了包括RP在内的所有预定治疗。3级毒性包括4例（13%）患者无症状肝功能检查升高，1例（3%）患者腹泻，1例（3%）患者疲劳。1例患者出现4级毒性，丙氨酸转氨酶升高。RP标本病理显示所有病例均有残留癌。29例（94%）患者达到临床部分缓解，其中35%的患者在eMRI上显示影像学改善。
31例接受多西他赛和吉非替尼治疗的患者未观察到病理完全缓解。这种联合治疗耐受性良好，且未导致手术并发症增加。
