Ikuo Nomura

Early monocytopenia after chemotherapy as a risk factor for neutropenia.

Neutropenia is a major adverse effect of cancer chemotherapy and sometimes causes life-threatening events. The present study was therefore conducted to identify risk factors for such neutropenia. Forty patients who had received chemotherapy at 3- or 4-week intervals for advanced lung cancer from May 1991 through February 1997 were analyzed retrospectively. Thirty-seven of the patients had received cisplatin-based chemotherapy. The mean neutrophil count on days 6 to 8 in 32 patients who developed grade 3 or 4 neutropenia during chemotherapy was not significantly different from that in eight patients who developed grade 1 or 2 neutropenia during chemotherapy. However, the mean leukocyte and monocyte counts on days 6 to 8 in the 32 patients with grade 3 or 4 neutropenia (5,181 +/- 1,830/microl and 87 +/- 84/microl, respectively) were significantly lower than those in the eight patients with grade 1 or 2 neutropenia (7175 +/- 1671/microl and 248 +/- 127/microl, respectively; p = 0.008 and p = 0.0001). Moreover, all 30 patients with a monocyte count of less than 150/microl on days 6 to 8 had grade 3 or 4 neutropenia and 8 of 10 patients with a monocyte count of 150/microl or higher on days 6 to 8 had grade 1 or 2 neutropenia, despite the absence of a correlation between the leukocyte count on days 6 to 8 and the neutrophil nadir. We conclude that a monocyte count of less than 150/microl on days 6 to 8 may be a predictor of grade 3 or 4 neutropenia during cancer chemotherapy at 3- or 4-week intervals (sensitivity 94%, specificity 100%).

Dose Escalation Study of Paclitaxel in Combination with Fixed-Dose Irinotecan in Patients with Advanced Non-Small Cell Lung Cancer (JCOG 9807)

Background: Both irinotecan (CPT) and paclitaxel (Pac) are effective against non-small cell lung cancer (NSCLC), and besides, preclinical studies have demonstrated an additive or synergistic interaction between camptothecin and taxane. Methods: We conducted a phase I/II study of combination chemotherapy consisting of Pac and CPT to determine qualitative and quantitative toxicities and efficacy of the combination against advanced NSCLC. We fixed the dose of CPT at 60 mg/m2 and escalated the Pac dose in 10 or 20 mg/m2 increments from a starting dose of 80 mg/m2, and repeated the cycle every 2 weeks. Prophylactic G-CSF was also administered. Results: Between February 1999 and April 2001, 24 patients were registered in the study. None of the patients had a history of prior chemotherapy, but surgical resection had been performed in 3 of them. None of the patients experienced dose-limiting toxicity (DLT) up to and including level 6. At dose level 7 of Pac, 180 mg/m2, 2 patients experienced DLT, that is grades 2 and 3 dyspnea due to pneumonitis. Another patient experienced grade 1 dyspnea due to pneumonitis. Neutropenia, diarrhea, and other toxicities were mild; however, we concluded that dose level 7 of Pac was the maximum-tolerated dose. An objective response was observed in 58.3%. The median survival time was 370 days, and the 1-year survival rate was 54.2%. Conclusion: Pneumonitis was the DLT in this study, and Pac 160 mg/m2 and CPT 60 mg/m2 every 2 weeks are recommended for the phase II study. This combination shows appreciable activity against NSCLC.

Prophylactic administration of granulocyte colony-stimulating factor when monocytopenia appears lessens neutropenia caused by chemotherapy for lung cancer.

In a retrospective study, we showed that a monocyte count of <150/microl on days 6 to 8 might be a predictor of grade III or IV neutropenia during cancer chemotherapy given at 3- or 4-week intervals. In the present study, we investigated whether the administration of granulocyte colony-stimulating factor (G-CSF) when monocytopenia appears lessens neutropenia during chemotherapy for lung cancer. Between June 1997 and August 1998, 60 patients who received chemotherapy at 3- or 4-week intervals for unresectable lung cancer were randomized to receive G-CSF (2 microg/kg or 50 microg/m2) when monocytopenia (<150/microl) appeared on days 6 to 8 after chemotherapy (group A) or when neutropenia (<1,000/microl) or leukopenia (<2,000/ microl) appeared after chemotherapy (group B). The administration of G-CSF was stopped when the leukocyte or neutrophil counts reached > 10,000/microl or 5,000/microl, respectively. The blood cells counts were examined three times a week and the degree, duration, and frequency of chemotherapy-induced neutropenia of the two groups were compared. One patient in group A was excluded because whole brain irradiation during chemotherapy was required. Twenty-nine and 30 patients in groups A and B, respectively, received platinum-based chemotherapy and their chemotherapy-induced hematologic toxicities were analyzed. The mean neutrophil count nadir of group A (1,558 +/- 1,771/microl) was significantly higher than that of group B (810 +/- 639/microl, p = 0.032). The duration of grade III neutropenia in group A (1.4 +/- 1.7 days) was significantly shorter than that in group B (2.9 +/- 1.9 days, p = 0.004), and the frequency of grade III neutropenia in group A (48%) was significantly lower than that in group B (83%, p = 0.002). Infectious episodes occurred in five and eight patients in groups A and B, respectively. The durations of G-CSF therapy required by group A and B patients (4.8 +/- 3.1 vs. 4.7 +/- 2.7 days) were not significantly different. Prophylactic administration of G-CSF did not exacerbate anemia or thrombocytopenia induced by chemotherapy. We conclude that the prophylactic administration of G-CSF when monocytopenia appears can lessen neutropenia caused by chemotherapy for lung cancer without increasing the total G-CSF dose.

Chest Wall Involvement by Lung Cancer: Thin-section Computed Tomography Based on Radiologic-Pathologic Correlation.

肺癌の胸壁浸潤診断の精度を高める目的で, 通常CT画像および造影thin-section CT画像とその病理所見を対比検討した. 対象は最近約3年間に神奈川県立がんセンターにおいて切除された原発性肺癌240例の中で, 通常CT画像で胸壁浸潤が疑われた33例である. 使用したCT機種は東芝製TCT-900S, HELIXであり, 術前2週間以内に60mlの造影剤で通常CTを撮影した後, 関心領域をhelical CTで40mlの造影剤を用い撮影した. 再構成した画像は10mm厚, 10mm間隔の通常CT画像と2mm厚, 2mm間隔のthin-section CT画像であり, WL40, WW400の縦隔条件画像と病理所見を対比した. 通常CT画像での胸壁浸潤診断の正診率は48%であったが, thin-section CT画像を併用するとそれは82%に上昇した. 以上より, 通常造影CT画像に造影thin-section CT画像を併用することは, より正確な肺癌のT因子診断に寄与できることが示唆された.

Computed Tomography Imaging Analysis of Resected Lung Cancers Detected by Computed Tomography.

最近約3年間に神奈川県立がんセンターで切除された原発性肺癌240例の中で, 通常の胸部単純X線写真ではその原発巣の指摘が困難でX線CT検査を契機に発見された肺野型肺癌30例について, CT画像および病理所見をretrospectiveに解析した.内訳は男性16例, 女性14例であり, 年齢は39～79 (中央値66) 歳であった.発見動機は自覚症状を有した例は5例のみであり, 他疾患経過中が8例, 残りは検診を目的としてCTが施行された.CT画像は淡い低濃度型と辺縁明瞭な充実型に大別され, 前者では病変と既存肺野との濃度差が少ないことが, 後者では肺門部の血管, 心臓および骨組織との重なりによりX線写真では病変の描出が困難であった.病理所見は25例 (83%) が1期であり, うち低濃度型例が21例 (70%) を占めた.以上よりCTで発見された肺癌, 特に低濃度型例は早期肺癌が多く, CT検査の検診への導入と低濃度型例の発見が治癒する肺癌の発見につながることが示唆された.