Wolff R A, Evans D B, Gravel D M, Lenzi R, Pisters P W, Lee J E, Janjan N A, Charnsangavej C, Abbruzzese J L
The Pancreatic Tumor Study Group, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Clin Cancer Res. 2001 Aug;7(8):2246-53.
Gemcitabine has modest activity in the treatment of advanced pancreatic cancer and is a potent radiosensitizer. We conducted a Phase I trial to determine the maximum tolerated dose of weekly gemcitabine delivered concurrently with radiation therapy for the treatment of locally advanced adenocarcinoma of the pancreatic head and to assess the treatment-related toxic effects associated with such a regimen. Eighteen patients with pathologically proven, locally advanced adenocarcinoma of the pancreatic head were enrolled in this study. Patients received seven weekly doses of gemcitabine with 3000 cGy of external beam radiation therapy delivered during the first 2 weeks of therapy. Six patients received gemcitabine at 350 mg/m(2)/week, nine at 400 mg/m(2)/week, and three at 500 mg/m(2)/week. Grade 3-4 hematological toxicity was observed in over half the patients treated. Nonhematological toxicities were significant and included fatigue, anorexia, nausea, vomiting, and dehydration. Forty-four % of the patients required admission to the hospital for management of nausea/vomiting and dehydration. The risk of hospitalization appeared to be dose-related; all of the three patients treated at 500 mg/m(2)/week required hospital admission during treatment. Seventeen patients were evaluated for response, and eight patients (47%) had evidence of a local anticancer effect. Four of these eight patients (24%) had a partial response to therapy. The median survival for the entire group was 6 months. The 1-year survival rate for patients with an objective response to therapy was 66%. The clinical responses observed in this group of patients suggest gemcitabine is a clinically relevant radiosensitizer in patients with pancreatic adenocarcinoma. However, the toxic effects are significant, suggesting that until dose and scheduling issues are explored further, concomitant administration of gemcitabine and radiation therapy should still be considered investigational.
吉西他滨在晚期胰腺癌治疗中活性一般，但它是一种有效的放射增敏剂。我们开展了一项I期试验，以确定每周一次吉西他滨与放射治疗同时应用时治疗局部晚期胰头腺癌的最大耐受剂量，并评估该方案相关的治疗毒性。18例经病理证实为局部晚期胰头腺癌的患者入组本研究。患者在治疗的前2周接受7次每周剂量的吉西他滨，同时接受3000 cGy的外照射放疗。6例患者接受350 mg/m²/周的吉西他滨，9例接受400 mg/m²/周，3例接受500 mg/m²/周。超过半数接受治疗的患者出现3 - 4级血液学毒性。非血液学毒性显著，包括疲劳、厌食、恶心、呕吐和脱水。44%的患者因恶心/呕吐和脱水需要住院治疗。住院风险似乎与剂量相关；接受500 mg/m²/周治疗的3例患者在治疗期间均需住院。17例患者接受疗效评估，8例患者（47%）有局部抗癌效果证据。这8例患者中有4例（24%）对治疗有部分缓解。整个组的中位生存期为6个月。对治疗有客观反应的患者1年生存率为66%。该组患者观察到的临床反应表明吉西他滨在胰腺腺癌患者中是一种具有临床意义的放射增敏剂。然而，毒性显著，这表明在进一步探索剂量和给药方案问题之前，吉西他滨与放射治疗的联合应用仍应被视为试验性的。
