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Katsuyuki Hotta,
Etsuji Suzuki,
Massimo Di Maio,
Paolo Chiodini,
Yoshiro Fujiwara,
Nagio Takigawa,
Eiki Ichihara,
Martin Reck,
Christian Manegold,
Lothar Pilz,
Akiko Hisamoto-Sato, Masahiro Tabata,
Mitsune Tanimoto,
Frances A Shepherd,
Katsuyuki Kiura
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ABSTRACT: BACKGROUND: We examined how crossover therapy might affect the association between progression-free survival (PFS) and overall survival (OS) in non-small cell lung cancer (NSCLC). METHODS: We extracted PFS- and OS-hazard ratios (HRs) in phase III trials of molecular-targeted agents for advanced NSCLC. Their relationship was modeled in a linear function with the coefficient of determination (R-squared) to assess the correlation between PFS and OS. RESULTS: Thirty-four trials with 35 pairs for the investigational and reference arms were identified (24,158 patients). Overall, there was little correlation between PFS- and OS-HRs (R-squared=0.14), suggesting PFS-HR could account only for 14% of variation in OS-HR. The median proportion of crossover therapy per trial was 20%. If patients seldom crossed over (none or <1%), the association between PFS- and OS-HRs was strong (R-squared=0.69). When the proportion of crossover was ≥1%, however, R-squared declined considerably (≥1% to <20% crossover, R-squared=0.27; ≥20% to <40%, R-squared=0.06; and ≥40%, R-squared=0.27). CONCLUSIONS: A PFS advantage seldom is associated with an OS advantage any longer. Our analysis suggests this is due to a high level of crossover now that an increasing number of active agents are available for NSCLC.
Lung cancer (Amsterdam, Netherlands) 11/2012; · 3.14 Impact Factor
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ABSTRACT: Chemoradiotherapy (CHRT) yields a favorable antitumor activity in patients with limited-stage small-cell lung cancer (LD-SCLC) with a response rate of around 80%. Even in such responders, the majority recur, indicating the importance of identifying a subset of patients with a poor outcome earlier through the treatment. We investigated whether the timing of obtaining tumor regression with the CHRT could affect the prognosis in LD-SCLC patients who finally achieved the objective response through the treatment.
We retrospectively reviewed medical charts of 70 LD-SCLC patients who obtained complete response (CR) or partial response (PR) with the 3 or 4 cycles of first-line CHRT between 1988 and 2006.
In the whole 70 patients with CR/PR, the median survival time and median progression free survival (PFS) were 39.6 and 12.3months, respectively. Fifty-two (74.3%) of the 70 patients entered CR/PR after the first cycle of CHRT, and their 2-year survival rates were significantly longer than that in the remaining 18 patients without entering CR/PR yet at the end of first cycle (72.3% and 7.1%, respectively, p<0.001). Cox regression analysis showed that the early response to the treatment was a significant prognostic factors (hazard ratio=0.098; 95% confidence interval=0.036-0.269). Regarding PFS, similar findings were observed.
Patients without entering CR/PR yet after the first course had a poorer outcome even though the objective response was finally confirmed through the treatment. Development of more effective treatments for these high-risk patients is warranted to improve their poor prognosis.
Lung cancer (Amsterdam, Netherlands) 07/2012; 78(1):107-11. · 3.14 Impact Factor
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Nihon Naika Gakkai Zasshi 05/2012; 101(5):1386-8.
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Naoyuki Nogami,
Katsuyuki Hotta,
Yoshihiko Segawa,
Nagio Takigawa,
Shinobu Hosokawa,
Isao Oze,
Masanori Fujii,
Eiki Ichihara,
Takuo Shibayama,
Atsuhiko Tada,
Noboru Hamada,
Masatoshi Uno,
Akihiko Tamaoki,
Shoichi Kuyama,
Genyo Ikeda,
Masahiro Osawa,
Saburo Takata, Masahiro Tabata,
Mitsune Tanimoto,
Katsuyuki Kiura
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ABSTRACT: The survival advantage achieved by existing anti-cancer agents as second-line therapy for relapsed non-small cell lung cancer (NSCLC) is modest and further improvement of treatment outcome is desired. Combination chemotherapy with irinotecan and amrubicin for advanced NSCLC has not been fully evaluated.
The primary endpoint of this phase II clinical trial was objective response. Patients with NSCLC who had been treated previously with one or two chemotherapy agents were enrolled. Irinotecan and amrubicin were both administered on Days 1 and 8 of a 21-day cycle, at doses of 100 mg/m(2) and 40 mg/m(2), respectively.
Between 2004 and 2006, 31 patients received a total of 101 courses; the median number of courses administered was three (range, one to six). Objective response was obtained in nine of the 31 patients (29.0% response rate; 95% confidence interval (CI), 12.1-46.0%). With a median follow-up time of 43.9 months, median survival time and the median progression-free survival time were 14.2 and 4.0 months, respectively. Myelosuppression was the most frequently observed adverse event, with grade 3/4 neutropenia in 51% of patients. Febrile neutropenia developed after nine courses (9%) and resulted in one treatment-related death. Cardiac toxicity and diarrhea, possibly specific for both agents, were infrequent and manageable.
Combination chemotherapy with irinotecan and amrubicin is effective in patients with NSCLC but showed moderate toxicities in second- or third-line settings.
Acta oncologica (Stockholm, Sweden) 01/2012; 51(6):768-73. · 2.27 Impact Factor
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Saeko Ozaki,
Nagio Takigawa,
Eiki Ichihara,
Katsuyuki Hotta,
Isao Oze,
Etsuko Kurimoto,
Soichiro Fushimi,
Tetsuya Ogino, Masahiro Tabata,
Mitsune Tanimoto,
Katsuyuki Kiura
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ABSTRACT: Heavily treated Wilms' tumor responding to the combination of paclitaxel and carboplatin has not yet been reported.
A 17-year-old man presented with hematuria. He received a diagnosis of Wilms' tumor with multiple lung metastases and was treated with preoperative chemotherapy including vincristine, dactinomycin, and doxorubicin, a right nephrectomy, and adjuvant chemotherapy, followed by pulmonary metastasectomy. During the next 8 years, he suffered from 4 relapses and has been treated with multiple anticancer agents including high-dose chemotherapy with autologous peripheral blood stem cell transplantation. Finally, the disease progressed due to peritoneal and pleural metastases. With opioid administration for left shoulder pain due to pleural metastasis, he received combination chemotherapy with carboplatin (area under the curve = 4) and paclitaxel (175 mg/m(2)) on day 1. After 2 cycles, he achieved a partial response with mild toxicity. He received 7 cycles of the chemotherapy and the time to progression was 200 days.
In a refractory case after intensive treatments, we succeeded to control the disease for a while.
Onkologie 01/2012; 35(5):283-6. · 0.87 Impact Factor
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ABSTRACT: Treatment-related death (TRD) remains a serious problem in small-cell lung cancer (SCLC), despite recent improvements in supportive care. However, few studies have formally assessed time trends in the proportion of TRD over the past two decades. The aim of this study was to determine the frequency and pattern of TRD over time.
We examined phase 3 trials conducted between 1990 and 2010 to address the role of systemic treatment for SCLC. The time trend was assessed using linear regression analysis.
In total, 97 trials including nearly 25,000 enrolled patients were analyzed. The overall TRD proportion was 2.95%. Regarding the time trend, while it was not statistically significant, it tended to decrease, with a 0.138% decrease per year and 2.76% decrease per two decades. The most common cause of death was febrile neutropenia without any significant time trend in its incidence over the years examined (p = 0.139). However, deaths due to febrile neutropenia as well as all causes in patients treated with non-platinum chemotherapy increased significantly (p = 0.033).
The overall TRD rate has been low, but not negligible, in phase III trials for SCLC over the past two decades.
PLoS ONE 01/2012; 7(8):e42798. · 4.09 Impact Factor
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ABSTRACT: Pemetrexed (PEM), a multitargeted antifolate with manageable toxicity, is active against non-squamous non-small cell lung cancer; however, most patients eventually acquire resistance to PEM. To elucidate the resistant mechanism, we established PEM-resistant lung adenocarcinoma cell lines. Two parental cell lines, PC-9 and A549, were treated with step-wise increasing concentrations of PEM. Growth inhibition was determined by the 3-[4,5-dimethyl-thizol-2-yl]-2,5-diphenyltetrazolium bromide assay. Expression of the genes encoding thymidylate synthase (TS), dihydrofolate reductase (DHFR), and glycinamide ribonucleotide formyltransferase (GARFT) was analyzed by quantitative real-time reverse transcriptase polymerase chain reaction. The four PC-9 sublines were more resistant than the PC-9 cell line to PEM (2.2-, 2.9-, 8.4-, and 14.3-fold, respectively). The four A549 sublines also showed more resistance to PEM (7.8-, 9.6-, 42.3-, and 42.4-fold, respectively) than the parent cell line. All resistant sublines showed cross-resistance to cisplatin, but not to docetaxel, vinorelbine, 5-fluorouracil, or the active metabolite of irinotecan, SN-38. All PEM-resistant sublines expressed more TS than the parental cells, by polymerase chain reaction and Western blotting. DHFR was significantly increased in the four PEM-resistant A549 sublines. GARFT did not correlate with resistance to PEM. In summary, PEM-resistant cells remained sensitive to docetaxel, vinorelbine, 5-fluorouracil, and irinotecan. TS expression appeared to be associated with resistance to PEM.
Cancer letters 10/2011; 309(2):228-35. · 4.86 Impact Factor
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Nagio Takigawa,
Katsuyuki Kiura,
Yoshihiko Segawa,
Katsuyuki Hotta,
Akihiko Tamaoki,
Yoshiyuki Tokuda,
Takuya Nagata,
Kazuhiko Watanabe,
Kenichi Gemba,
Tomonori Moritaka,
Naokatsu Horita,
Hiromasa Takeda,
Niro Okimoto,
Mitsuhiro Takemoto,
Keitaro Matsuo,
Tetsu Shinkai, Masahiro Tabata,
Hiroshi Ueoka,
Susumu Kanazawa,
Mitsune Tanimoto
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ABSTRACT: Thoracic radiotherapy (RT) with concurrent chemotherapy may be offered to selected elderly patients with locally advanced non-small cell lung cancer. The Okayama Lung Cancer Study Group (OLCSG) 0007 trial with patients up to 75 years showed that with concurrent RT, docetaxel and cisplatin (DP) chemotherapy was an alternative to mitomycin C, vindesine, and cisplatin (MVP) chemotherapy.
Of the 99 patients in the DP arm, 73 were younger than 70 years and 26 were 70 years or older. Of the 101 patients in the MVP arm, 75 were younger than 70 years and 26 were 70 years or older. Overall survival (OS) and progression-free survival (PFS) were calculated using the Kaplan-Meier method and were compared using an early period weighted log-rank test. Toxicities and treatment intensities were compared by χ(2) and t tests, respectively.
OS and PFS tended to be longer in the DP arm versus MVP arm: median OS (months), 27.5 versus 22.9 (p = 0.109) and 25.6 versus 23.4 (p = 0.064) in the ≥70-year and <70-year groups, respectively; median PFS (months), 19.0 versus 11.5 (p = 0.175) and 12.0 versus 9.3 (p = 0.132) in the ≥70-year and less than 70-year groups, respectively. Severe toxicity (neutropenia, esophagitis, and pneumonitis) rates did not differ between age groups. Nevertheless, the absence of statistically significant differences in this retrospective analysis might be due to the small number of patients. Radiation intensity was similar between the groups, but chemotherapy intensity was lower in the ≥70-year group.
Chemotherapy with concurrent RT may be effective and tolerable in elderly patients with locally advanced non-small cell lung cancer.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 03/2011; 6(6):1087-91. · 4.55 Impact Factor
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Naoyuki Nogami,
Katsuyuki Hotta,
Shoichi Kuyama,
Katsuyuki Kiura,
Nagio Takigawa,
Kenichi Chikamori,
Takuo Shibayama,
Daizo Kishino,
Shinobu Hosokawa,
Akihiko Tamaoki,
Shingo Harita, Masahiro Tabata,
Hiroshi Ueoka,
Tetsu Shinkai,
Mitsune Tanimoto
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ABSTRACT: Chemotherapy is a mainstay in the treatment of extensive-disease small-cell lung cancer (ED-SCLC), although the survival benefit remains modest. We conducted a phase II trial of amrubicin (a topoisomerase II inhibitor) and topotecan (a topoisomerase I inhibitor) in chemotherapy-naïve and relapsed SCLC patients.
Amrubicin (35 mg/m(2)) and topotecan (0.75 mg/m(2)) were administered on days 3-5 and 1-5, respectively. The objective response rate (ORR) was set as the primary endpoint, which was assessed separately in chemotherapy-naïve and relapsed cases.
Fifty-nine patients were enrolled (chemotherapy-naïve 31, relapsed 28). The ORRs were 74% and 43% in the chemotherapy-naïve and relapsed cases, respectively. Survival data were also promising, with a median progression-free survival time and median survival time of 5.3 and 14.9 months and 4.7 and 10.2 months in the chemotherapy-naïve and relapsed cases, respectively. Even refractory-relapsed cases responded to the treatment favorably (27% ORR). The primary toxicity was myelosuppression with grades 3 or 4 neutropenia in 97% of the patients, which led to grades 3 or 4 febrile neutropenia in 41% of the patients and two toxic deaths.
This phase II study showed the favorable efficacy and moderate safety profiles of a topotecan and amrubicin two-drug combination especially in relapsed patients with ED-SCLC.
Lung cancer (Amsterdam, Netherlands) 02/2011; 74(1):80-4. · 3.14 Impact Factor
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ABSTRACT: In advanced non-small-cell lung cancer (NSCLC), with the increasing number of active compounds available in salvage settings, survival after progression to first-line chemotherapy seems to have improved. A literature survey was conducted to examine whether survival post-progression (SPP) has improved over the years and to what degree SPP correlates with overall survival (OS).
Median progression-free survival (MPFS) time and median survival time (MST) were extracted in phase III trials of first-line chemotherapy for advanced NSCLC. SPP was pragmatically defined as the time interval of MST minus MPFS. The relationship between MPFS and MST was modeled in a linear function. We used the coefficient of determination (r(2)) to assess the correlation between them. Seventy trials with 145 chemotherapy arms were identified. Overall, median SPP was 4.7 months, and a steady improvement in SPP was observed over the 20 years (9.414-day increase per year; p<0.001) in parallel to the increase in MST (11.253-day increase per year; p<0.001); MPFS improved little (1.863-day increase per year). Overall, a stronger association was observed between MST and SPP (r(2) = 0.8917) than MST and MPFS time (r(2) = 0.2563), suggesting SPP and MPFS could account for 89% and 25% of the variation in MST, respectively. The association between MST and SPP became closer over the years (r(2) = 0.4428, 0.7242, and 0.9081 in 1988-1994, 1995-2001, and 2002-2007, respectively).
SPP has become more closely associated with OS, potentially because of intensive post-study treatments. Even in advanced NSCLC, a PFS advantage is unlikely to be associated with an OS advantage any longer due to this increasing impact of SPP on OS, and that the prolongation of SPP might limit the original role of OS for assessing true efficacy derived from early-line chemotherapy in future clinical trials.
PLoS ONE 01/2011; 6(11):e26646. · 4.09 Impact Factor
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Katsuyuki Hotta,
Katsuyuki Kiura,
Nagio Takigawa,
Etsuji Suzuki,
Hiroshige Yoshioka,
Toshiaki Okada,
Daizo Kishino,
Hiroshi Ueoka,
Koji Inoue, Masahiro Tabata,
Mitsune Tanimoto
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ABSTRACT: The relationship between poor performance status (PS) and toxicity during chemotherapy is controversial. We examined this for erlotinib monotherapy in non-small cell lung cancer (NSCLC) patients.
Toxicity during the first month of therapy was recorded in 209 patients receiving erlotinib for NSCLC, and its association with PS was assessed.
Of 209 patients, 52, 115, 30 and 12 had a PS of 0, 1, 2 and 3-4, respectively. Treatment was discontinued in 26% of patients within 1 month, with a higher rate in poorer PS patients (17%, 25%, 37% and 42%). Discontinuation was predominantly due to disease progression, rather than adverse events, in both the whole cohort (82% vs. 18%) and the poorest PS subgroup (100% vs. 0%). Three, two, and four patients with a PS of 1, 2 and 3-4, respectively, died within 1 month; all six deaths of PS 2-4 patients were attributed to disease progression. Treatment interruption and dose reduction rates were similar among the subgroups. The principal adverse event was skin rash, with identical incidence in all PS subgroups.
Poor PS is unlikely to increase the risk for toxicity during erlotinib monotherapy, but was related to low compliance, probably because of disease progression rather than treatment-related toxicity.
Lung cancer (Amsterdam, Netherlands) 12/2010; 70(3):308-12. · 3.14 Impact Factor
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Katsuyuki Hotta,
Katsuyuki Kiura,
Nagio Takigawa,
Hiroshige Yoshioka,
Hidetoshi Hayashi,
Hajime Fukuyama,
Akihiro Nishiyama,
Toshihide Yokoyama,
Shoichi Kuyama,
Shigeki Umemura,
Yuka Kato,
Naoyuki Nogami,
Yoshihiko Segawa,
Masayuki Yasugi, Masahiro Tabata,
Mitsune Tanimoto
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ABSTRACT: This study explores patient preferences for involvement in lung cancer treatment decisions and the extent of concordance between the views of patients and physicians on decisional roles. The impact of demographic and psychosocial characteristics on the decisional role of patients is also examined.
Patients with relapsed non-small cell lung cancer who were candidates for a phase II trial of erlotinib monotherapy were recruited. Patients were interviewed after they had learned of their relapse and the treatment decision had been made but before pharmacologic intervention.
Most of the 28 participants were married, had a smoking history, and were well educated. They reported moderate levels of depression and anxiety. Initially, 14% of the patients reported a preference for active decision making; later, 29% believed that the primary responsibility for the treatment decision had been theirs. Only 54% of the patients agreed with the physician's assessment of how the treatment decision was made (κ = 0.31; test of symmetry, p = 0.23). The depression score was significantly associated with a patient's preferred level of control (p < 0.01).
The limited concordance between patient preference and perception and between patient and physician perceptions regarding how the treatment decision was made suggests that physicians should more accurately identify patient preferences by directly asking patients at the beginning of each clinical encounter.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 10/2010; 5(10):1668-72. · 4.55 Impact Factor
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Yoshihiko Segawa,
Katsuyuki Kiura,
Katsuyuki Hotta,
Nagio Takigawa, Masahiro Tabata,
Keitaro Matsuo,
Hiroshige Yoshioka,
Hidetoshi Hayashi,
Haruyuki Kawai,
Keisuke Aoe,
Tadashi Maeda,
Hiroshi Ueoka,
Mitsune Tanimoto
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ABSTRACT: The survival impact of single-agent treatment with docetaxel, the standard regimen for relapsed patients with non-small cell lung cancer (NSCLC), remains modest. We conducted a randomized phase II study to evaluate the efficacy and safety of the combination of docetaxel and S-1 in the second-line setting.
Patients with relapse of NSCLC after first-line platinum-based chemotherapy were randomly assigned to docetaxel alone (60 mg/m, day 1, q3 weeks; arm A) or a combination of docetaxel (40 mg/m, day 1, q3 weeks) and S-1 (80 mg/m, days 1-15; arm B). The primary end point was response rate, whereas secondary endpoints included overall survival, progression-free survival, and toxicity.
Between 2005 and 2008, a total of 60 patients were enrolled in the study. The objective response rates were 20.7% and 16.1% in arms A and B, respectively (p = 0.81). Progression-free survival was comparable in the two arms (median: 3.7 versus 3.4 months, p = 0.27), whereas overall survival time was longer in arm A (22.9 versus 8.7 months, p = 0.02). The major toxicity was myelosuppression with grade > or =3 neutropenia in 89.7% of patients versus 64.5% in arms A and B, respectively.
This study suggests that docetaxel monotherapy should continue to be considered the standard for second-line chemotherapy against NSCLC.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 09/2010; 5(9):1430-4. · 4.55 Impact Factor
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Yoshihiko Segawa,
Katsuyuki Kiura,
Nagio Takigawa,
Haruhito Kamei,
Shingo Harita,
Shunkichi Hiraki,
Yoichi Watanabe,
Keisuke Sugimoto,
Takuo Shibayama,
Toshiro Yonei,
Hiroshi Ueoka,
Mitsuhiro Takemoto,
Susumu Kanazawa,
Ichiro Takata,
Naoyuki Nogami,
Katsuyuki Hotta,
Akio Hiraki, Masahiro Tabata,
Keitaro Matsuo,
Mitsune Tanimoto
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ABSTRACT: To demonstrate the efficacy of docetaxel and cisplatin (DP) chemotherapy with concurrent thoracic radiotherapy (TRT) for patients with locally advanced non-small-cell lung cancer (LA-NSCLC).
Patients age 75 years or younger with LA-NSCLC, stratified by performance status, stage, and institution, were randomly assigned to two arms consisting of DP (docetaxel 40 mg/m(2) and cisplatin 40 mg/m(2) on days 1, 8, 29, and 36) or mitomycin, vindesine, and cisplatin (MVP) chemotherapy with concurrent TRT.
Between July 2000 and July 2005, 200 patients were allocated into either the DP or MVP arm. The survival time at 2 years, a primary end point, was favorable to the DP arm (P = .059 by a stratified log-rank test as a planned analysis and P = .044 by an early-period, weighted log-rank as an unplanned analysis). There was a trend toward improved response rate, 2-year survival rate, median progression-free time, and median survival in the DP arm (78.8%, 60.3%,13.4 months, and 26.8 months, respectively) compared with the MVP arm (70.3%, 48.1%, 10.5 months, and 23.7 months, respectively), which was not statistically significant (P > .05). Grade 3 febrile neutropenia occurred more often in the MVP arm than in the DP arm (39% v 22%, respectively; P = .012), and grade 3 to 4 radiation esophagitis was likely to be more common in the DP arm than in the MVP arm (14% v 6%, P = .056).
DP chemotherapy combined with concurrent TRT is an alternative to MVP chemotherapy for patients with LA-NSCLC.
Journal of Clinical Oncology 07/2010; 28(20):3299-306. · 18.37 Impact Factor
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ABSTRACT: We describe a rare case of primary mediastinal large cell neuroendocrine carcinoma (LCNEC) with brain metastases. A 65-year-old man presented with a mediastinal abnormal shadow on chest radiography. A computed tomography-guided needle biopsy of the mediastinal tumor revealed malignant cells. After biopsy, dyspnea, leg weakness and a waddling gait rapidly developed. Magnetic resonance imaging of the brain revealed three masses with ring enhancements. His pro-GRP value was 95.5 pg/ml. Since the cerebellar tumor extended to the brain stem, it was removed surgically. The brain tumor demonstrated LCNEC. He received systemic chemotherapy of cisplatin and irinotecan, because his leg weakness and waddling gait had improved markedly after surgery followed by whole brain irradiation.
Nihon Kokyūki Gakkai zasshi = the journal of the Japanese Respiratory Society. 07/2010; 48(7):506-10.
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Nagio Takigawa,
Katsuyuki Kiura,
Katsuyuki Hotta,
Shinobu Hosokawa,
Naoyuki Nogami,
Keisuke Aoe,
Kenichi Gemba,
Keiichi Fujiwara,
Shingo Harita,
Mitsuhiro Takemoto,
Kengo Himei,
Tetsu Shinkai,
Yoshirou Fujiwara,
Saburo Takata, Masahiro Tabata,
Susumu Kanazawa,
Mitsune Tanimoto
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ABSTRACT: S-1, an oral 5-fluorouracil derivative, is effective against advanced non-small cell lung cancer (NSCLC) with mild toxicity and synergistic effects with radiation in preclinical trials. In this phase I study, we evaluated the dose-limiting toxicity and recommended dose of S-1 for a future phase II study when administered concurrently with thoracic radiation (total dose of 60 Gy at 2 Gy per daily fraction) in elderly patients (>75 years old) with localized advanced NSCLC. S-1 was administered on days 1-14 and 29-42 at the following dosages: 60, 70, and 80 mg/m(2)/day. Twenty-two previously untreated patients were enrolled in this study. Dose-limiting toxicity included febrile neutropenia, thrombocytopenia, stomatitis, and pneumonitis. One patient had grade 5 radiation pneumonitis. No other patient experienced radiation pneumonitis or esophagitis exceeding grade 2. The recommended dose for S-1 was determined to be 80 mg/m(2)/day, which produced an overall response rate of 75% (n=12). The median progression-free survival time was 11.5 months (95% confidence interval: 7.1-15.8 months) with a median follow-up time of 27.9 months. These results indicate that concurrent treatment with S-1 and thoracic radiation is a feasible option for NSCLC in the elderly. A phase II study is currently under way.
Lung cancer (Amsterdam, Netherlands) 05/2010; 71(1):60-4. · 3.14 Impact Factor
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ABSTRACT: We examined the feasibility of triplet chemotherapy using cisplatin, docetaxel, and irinotecan for patients with recurrent or refractory non-small cell lung cancer (NSCLC), retrospectively. Twenty-five patients (21 men and 4 women) with NSCLC and good performance status who were < or = 70 years old were analyzed. The median age was 58 years. Most patients had performance status 1 (16/25), stage IV disease (18/25) and adenocarcinoma-histology (16/25). Cisplatin and docetaxel were given on day 1 and irinotecan on day 2; the cycle was repeated every 3 weeks. The objective response rate was 39.1% (95% confidence interval: 18.7-59.5%). The median survival time and actual 2-, 3-, and 5-year survival rates were 14.3 months, 32%, 20%, and 8%, respectively. Of note, only 6 patients were treated with gefitinib at the recurrence after triplet chemotherapy; of these, 4 (67%) achieved a partial response, which might result in favorable survival. Grade 3/4 toxicities consisted of neutropenia (100%), neutropenic fever (56%), nausea/vomiting (40%), and diarrhea (16%); no cases of treatment-related death occurred. Triplet chemotherapy showed impressive survival data in our clinical trial, but proved too toxic for use in treating patients with NSCLC in the clinical practice.
Acta medica Okayama 02/2010; 64(1):33-7. · 0.84 Impact Factor
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Katsuyuki Hotta,
Katsuyuki Kiura,
Nagio Takigawa,
Hiroshige Yoshioka,
Shingo Harita,
Shoichi Kuyama,
Toshiro Yonei,
Keiichi Fujiwara,
Tadashi Maeda,
Keisuke Aoe,
Hiroshi Ueoka,
Haruhito Kamei,
Shigeki Umemura,
Tomonori Moritaka,
Yoshihiko Segawa,
Haruyuki Kawai,
Akihiro Bessho,
Katsuya Kato, Masahiro Tabata,
Mitsune Tanimoto
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ABSTRACT: Data comparing the incidence and pattern of interstitial lung disease (ILD) in non-small cell lung cancer patients receiving treatment with gefitinib versus erlotinib, both of which are epidermal growth factor receptor tyrosine kinase inhibitors, are scarce. We investigated the incidence of ILD in Japanese patients treated with gefitinib or erlotinib.
We reviewed the clinical records of 209 patients treated with erlotinib in 2008 (cohort A) and 330 treated with gefitinib between 2000 and 2003 (cohort B). Toxicity within the first month of treatment was investigated.
The patients in cohort A had fewer known risk factors for ILD (e.g., poor performance status and prior pulmonary fibrosis). ILD was detected in two patients (1.0%) from cohort A and eight patients (2.4%) from cohort B during the first month of treatment. The events were graded as follows: one patient each in grades 1 and 2 (cohort A), and one, one, and six patients in grades 3, 4, and 5, respectively (cohort B). Multivariate analysis revealed that poor performance status and prior pulmonary fibrosis were significantly correlated with the occurrence of ILD, but the type of epidermal growth factor receptor tyrosine kinase inhibitor administered was not.
There was a somewhat lower incidence of ILD with erlotinib therapy than with gefitinib therapy, despite no statistically significant difference. Patient selection based on awareness by Japanese physicians of the risk factors for ILD, rather than the type of agent, may explain the difference in ILD incidence between the two treatments.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 02/2010; 5(2):179-84. · 4.55 Impact Factor
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Hiroshige Yoshioka,
Katsuyuki Hotta,
Katsuyuki Kiura,
Nagio Takigawa,
Hidetoshi Hayashi,
Shingo Harita,
Shoichi Kuyama,
Yoshihiko Segawa,
Haruhito Kamei,
Shigeki Umemura,
Akihiro Bessho, Masahiro Tabata,
Mitsune Tanimoto
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ABSTRACT: Efficacy of gefitinib therapy strongly depends on epidermal growth factor receptor (EGFR)-mutation status in Asian patients with non-small cell lung cancer. Recently, the survival advantage of erlotinib, another tyrosine kinase inhibitor, was not affected by EGFR mutation status in a phase III trial, indicating that patients with EGFR-wild-type (EGFR-wt) tumors might also benefit from this tyrosine kinase inhibitor. The aim of this trial was to evaluate the efficacy and toxicity of erlotinib in Japanese patients with EGFR-wt tumors.
The primary end point was an objective response. Patients with EGFR-wt tumors previously receiving one to three chemotherapy regimens were enrolled in this trial. The mutation status was assessed using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method. Erlotinib was administered (150 mg/d) until disease progression or unacceptable toxicities occurred.
Thirty patients were enrolled between January and December 2008. Objective response was observed in one patient (3.3%), and the disease became stable in 18 patients (60.0%). Skin rash was the most common side effect. Grades 3-4 adverse events included pulmonary embolism, keratitis, and anemia. Two other patients developed interstitial lung disease (grades 1 and 2). Nevertheless, all these events were reversible, resulting in no treatment-related deaths. With a median follow-up time of 10.7 months, the median survival time and median progression-free survival times were 9.2 and 2.1 months, respectively.
This is the first prospective biomarker study showing that erlotinib therapy for pretreated patients with EGFR-wt tumors seems to have a modest activity with no irreversible toxicity.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 11/2009; 5(1):99-104. · 4.55 Impact Factor
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ABSTRACT: With the increasing number of active compounds available for advanced non-small cell lung cancer, it is useful to evaluate whether surrogate end points can replace survival in randomized trials for the rapid and efficient assessment of efficacy. We examined the association between differences in overall survival and time to progression (TTP) using a literature survey.
We used median TTP (MTTP) and median survival time (MST) from 54 phase III trials of first-line chemotherapy involving 23,457 advanced non-small cell lung cancer patients in a multiple linear regression analysis. The MST ratio in each trial was defined as the ratio of MST in the investigational arm to that in the reference arm. The MTTP ratio was defined similarly.
The degree of the association between the MST and MTTP ratios was only moderate both in the overall cohort (R(2) = 0.33) and various trial settings (R(2) = 0.16-0.51), although the MTTP ratio was an independent factor influencing the MST ratio in the multiple regression model (p < 0.01). This means that the MTTP ratio could account for less than half of the variance in the MST ratio.
The TTP potentially acts as a surrogate marker, but may not be still a definitive alternative in the first-line setting.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 02/2009; 4(3):311-7. · 4.55 Impact Factor
