Japanese Journal of Clinical Oncology 31:299-304 (2001)
© 2001 Foundation for Promotion of Cancer Research
Recent Advances in the Chemotherapy of Non-small Cell Lung Cancer
Medical Oncology Division, National Cancer Center Hospital, Tokyo, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONCISPLATIN VERSUS CISPLATIN +...NOVEL AGENT + CISPLATIN...NOVEL AGENT + CISPLATIN...NOVEL AGENTS + CARBOPLATIN...REMAINING ISSUES AFFECTING...REFERENCES |
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Chemotherapeutic regimens containing new anticancer agents in combination with cisplatin and carboplatin have been demonstrated to be equivalently active against advanced non-small cell lung cancer. The choice of a chemotherapeutic regimen depends on differences in time to progression, response rate, toxicity profile, cost and symptom relief. Several other strategies, such as three-drug combinations, sequential use of a third drug, weekly administration, etc., have been evaluated to improve the chemotherapeutic effect. The sequencing of the human genome may permit targeting of specific abnormalities related to each lung cancer with target-based drugs. This should increase the possibility of application of individualized therapy and, we would hope, improve survival.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONCISPLATIN VERSUS CISPLATIN +...NOVEL AGENT + CISPLATIN...NOVEL AGENT + CISPLATIN...NOVEL AGENTS + CARBOPLATIN...REMAINING ISSUES AFFECTING...REFERENCES |
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Despite efforts to promote early detection and surgery, lung cancer remains the leading cause of cancer-related deaths in Japan. Advanced non-small cell lung cancer (NSCLC), stage IIIB and stage IV, accounts for the largest population in JCOG (Japanese Clinical Oncology Group) trials. Although the improvement of survival rate in advanced NSCLC has been modest during the past two decades, many clinical trials have demonstrated that cisplatin-based chemotherapy not only improves survival rates significantly in this population, but also that it provides symptom relief (1,2). Widely used chemotherapy regimens for NSCLC are etoposide + cisplatin (PE), in the USA, mitomycin C + ifosfamide + cisplatin (MIC), in Europe, and vindesine + cisplatin ± mitomycin C, in Japan. Many new active anticancer drugs have recently been introduced for the treatment of NSCLC (3,4). This paper reviews the integration of drugs into combined chemotherapy regimens and identifies issues that should be considered in clinical trials.
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CISPLATIN VERSUS CISPLATIN + NEW DRUGS |
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TOPABSTRACTINTRODUCTIONCISPLATIN VERSUS CISPLATIN +...NOVEL AGENT + CISPLATIN...NOVEL AGENT + CISPLATIN...NOVEL AGENTS + CARBOPLATIN...REMAINING ISSUES AFFECTING...REFERENCES |
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Several randomized trials have been conducted comparing cisplatin alone with cisplatin plus other drugs and in every study the combined chemotherapy regimen that included cisplatin yielded a better response rate (Table 1). Regimens which have been commonly used for more than 10 years, such as etoposide + cisplatin, however, did not show any survival benefit (5–7). Combined chemotherapy regimens that included new anticancer drugs were found to be superior to regimens containing cisplatin alone, except in a study by Gatzemeier and co-workers that compared cisplatin + paclitaxel versus cisplatin alone (8–11). Based on these results, combined chemotherapy regimens that include new anticancer drugs appear to provide superior survival benefits over regimens containing cisplatin alone.
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NOVEL AGENT + CISPLATIN VS CISPLATIN + ETOPOSIDE |
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TOPABSTRACTINTRODUCTIONCISPLATIN VERSUS CISPLATIN +...NOVEL AGENT + CISPLATIN...NOVEL AGENT + CISPLATIN...NOVEL AGENTS + CARBOPLATIN...REMAINING ISSUES AFFECTING...REFERENCES |
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Several randomized controlled trials have been performed comparing new combined chemotherapy regimens with cisplatin + etoposide (Table 2) (12–16).
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In an ECOG (Eastern Cooperative Oncology Group) trial (ECOG 5592) using high- and low-dose continuous infusion of paclitaxel, regimens containing paclitaxel + cisplatin yielded a clear improvement in overall survival (12). However, even this positive ECOG study required combining two paclitaxel subgroups into a single group to produce a statistically significant difference.
Belani et al. (13) conducted a similar randomized trial of carboplatin + paclitaxel vs cisplatin + etoposide but failed to demonstrate a survival advantage for the carboplatin + paclitaxel regimen. An EORTC trial of cisplatin + teniposide vs cisplatin + paclitaxel showed equivalent survival rates (14). Cisplatin + gemcitabine was compared with cisplatin + etoposide in a Spanish trial (15) and, although the response rate and time to progression were better in the gemcitabine group, the survival rates with the two regimens were not statistically different.
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NOVEL AGENT + CISPLATIN VS OTHER WIDELY USED REGIMENS |
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TOPABSTRACTINTRODUCTIONCISPLATIN VERSUS CISPLATIN +...NOVEL AGENT + CISPLATIN...NOVEL AGENT + CISPLATIN...NOVEL AGENTS + CARBOPLATIN...REMAINING ISSUES AFFECTING...REFERENCES |
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Table 3 shows the results of several randomized controlled trials which have compared a new agent-containing regimen with a widely used regimen. Two randomized controlled trials of regimens containing irinotecan have been conducted in Japan (17,18). One study showed a higher survival rate for irinotecan + cisplatin regimens than for vindesine + cisplatin regimens in stage IV patients (17), but there was no difference in survival rate between the two groups in the other study (18).
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Le Chevalier et al. (20) reported finding that vinorelbine + cisplatin was superior to their previous widely used regimen of cisplatin + vindesine. However, an Italian trial failed to demonstrate any improvement in survival when gemcitabine + cisplatin was compared with their standard regimen of mitomycin C + ifosfamide + cisplatin, although the response rate was significantly higher with the gemcitabine + cisplatin regimen (19).
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NOVEL AGENTS + CARBOPLATIN VS NOVEL AGENTS + CISPLATIN |
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TOPABSTRACTINTRODUCTIONCISPLATIN VERSUS CISPLATIN +...NOVEL AGENT + CISPLATIN...NOVEL AGENT + CISPLATIN...NOVEL AGENTS + CARBOPLATIN...REMAINING ISSUES AFFECTING...REFERENCES |
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Only a few randomized controlled trials have been conducted comparing carboplatin with cisplatin (Table 4) (24–27). A trial reported by Gatzemeier et al. (24) involving 618 patients (309 patients in each group) yielded the same response rate in both groups. The median survival period, however, was significantly longer in the group receiving cisplatin, although the 1-year survival rates in the two groups were not statistically different.
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Which of the various new combined chemotherapy regimens is most effective against advanced NSCLC?
At the ASCO 1999 meeting, SWOG reported the results of a randomized controlled trial comparing the efficacy and safety of two platinum-based chemotherapy combinations: vinorelbine + cisplatin vs paclitaxel + carboplatin (25). The trial population consisted of 410 patients and the response rate, median time to progression, median survival time and 1-year survival rate were identical in both groups (Table 4). The frequencies of grade 4 neutropenia and nausea/vomiting were higher in the vinorelbine + cisplatin group, whereas the frequency of neuropathy was higher in the carboplatin + paclitaxel group. Based on this study, SWOG adopted the paclitaxel + carboplatin regimen as a reference arm for future phase III studies because of the convenient dosing schedule and fewer trial withdrawals as a result of toxicity. Shiller et al.(26) reported the results of a randomized controlled trial involving four platinum-based regimens of ECOG 1594: paclitaxel + cisplatin (group A), gemcitabine + cisplatin (group B), docetaxel + cisplatin (group C) and paclitaxel + carboplatin (group D). The primary endpoints in this randomized trial were survival, response rate and time to progression. No significant differences were found in response rate, median survival or 1-year survival rate (Table 4), but the results in group B were superior to those in group A in terms of time to progression (4.5 vs 3.5 months, P = 0.002). Significantly fewer grade 4 toxicities occurred in group D than in group A (19 vs 25%), but more patients experienced progressive disease and stopped receiving treatment in group D than in group A. More patients experienced severe toxicity in group B than in group A.
The results of this study suggest that advances in platinum-based combined chemotherapy regimens for advanced NSCLC have reached their limit. Results superior to those reported by the ECOG will be extremely difficult to obtain.
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REMAINING ISSUES AFFECTING CHEMOTHERAPY REGIMENS FOR NSCLC |
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TOPABSTRACTINTRODUCTIONCISPLATIN VERSUS CISPLATIN +...NOVEL AGENT + CISPLATIN...NOVEL AGENT + CISPLATIN...NOVEL AGENTS + CARBOPLATIN...REMAINING ISSUES AFFECTING...REFERENCES |
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Three-drug Combinations
Three-drug combinations are being evaluated by a group in southern Italy, but the final results of the phase III study are not yet available (28,29). Although the data seem promising, the trials are somewhat problematic, because two randomized controlled trials of three-drug combinations were conducted during the same period, so there may have been a selection bias and the large discrepancy between the number of patients enrolled and the number of eligible patients suggests that their data may not have been obtained by intent-to-treat analysis. Thus, three-drug combinations are still unlikely to produce clinically meaningful advances.
Weekly Regimens
Weekly regimens are used in the treatment of NSCLC for two reasons: they enable researchers to determine the total dosage of chemotherapy that can be administered in conjunction with radiotherapy and the total dosage that can be given to elderly or frail patients.
Weekly regimens may make it possible to increase dose intensity and decrease the occurrence of adverse events (30–32). However, the data are still preliminary and questions remain as to whether weekly regimens are truly equivalently effective but less toxic than 3- to 4-week regimens.
Non-platinum Regimens
Platinum-based chemotherapy is the only form of chemotherapy known to have a survival benefit in patients with non-small cell lung cancer (1). Because of the availability of active anticancer drugs, clinical trials including non-platinum regimens are being considered and antitumor activity of gemcitabine + vinorelbine, docetaxel + vinorelbine and paclitaxel + gemcitabine regimens, etc., have been reported (33–38). Two randomized controlled trials, one comparing docetaxel + gemcitabine with docetaxel + cisplatin and the other comparing paclitaxel + gemcitabine with paclitaxel + carboplatin, have been reported by Kosmidis et al. (36) and Georgoulias et al. (37) and Takeda et al. (38) reported the results of a randomized trial comparing docetaxel + irinotecan with docetaxel + cisplatin (38). Although there were no differences in response rate, time to progression or median survival period between the regimens containing platinum and those that did not, the numbers of patients in these studies were too small to draw definitive conclusions. Whether non-platinum regimens are less toxic than platinum-based regimens also remains uncertain.
Regimens for Elderly and/or Frail Patients
The average age of lung cancer patients is 65 years. While US and European trials usually have no age limit, most Japanese trials only admit patients under 75 years old. Langer et al. (39) analyzed age as a risk factor in chemotherapy trials and found that the response, toxicity and survival rates of the elderly patients were similar to those of younger patients. However, patients over 70 years of age have a higher frequency of leukopenia and neuropsychological toxicity. There are only two randomized trials for elderly (>70 years) NSCLC patients reported by an Italian group (40,41), so relevant chemotherapy regimens for them remain uncertain. Meanwhile, SWOG and ECOG define poor-risk cases as exhibiting PS2 ± low albumin ± weight loss ± co-morbid disease and are conducting some clinical trials for that population. The average age of lung cancer patients in Japan is expected to increase to 75 years before 2015. Trials involving elderly and frail patients face several problems (40–45). Questions remain as to whether reduced dosages of anticancer drugs have equivalent antitumor activity and whether weekly regimens, non-platinum regimens or oral drugs are really less toxic and/or equivalently effective. Further clinical trials are essential to provide answers to these important questions.
Second-line Chemotherapy
Recently, many thoracic oncologists have been showing an interest in the antitumor activity of second-line chemotherapy regimens for advanced NSCLC. Shepherd et al. (46) and Fossella et al. (47) have shown that docetaxel is effective in previously treated NSCLC patients, and gemcitabine and paclitaxel have also been suggested to evoke antitumor responses in previously treated NSCLC patients (48,49,50). One explanation for the absence of significant differences in overall survival rates in the ECOG 1594 study may be that second-line therapy obscured any observable benefits and sequential use of single agents should be evaluated in the future. The usefulness of second-line therapies for metastatic lung cancer provides support for the argument in favor of sequential single-agent therapy.
Target-based Therapy
Numerous molecular targets of cancer chemotherapy have recently been identified as a result of advances in molecular biological research and many new categories of anticancer drugs have been developed for individual molecular targets. The molecular targets and strategies for each target in lung cancer are listed in Table 5. One example of this approach is a better understanding of growth-signaling pathways and it seems reasonable to develop specific agents that inhibit growth-factor receptors, receptor tyrosine kinases and downstream molecules. The epidermal growth factor pathway contributes to the malignant potential of non-small cell lung cancer. Approval has already been obtained for herceptin to treat HER-2/neu-positive breast cancer and ZD1839 (Iressa), a tyrosine kinase inhibitor, has shown strong antitumor activity against refractory non-small cell lung cancer. There is also evidence of synergy between target-based drugs and standard chemotherapeutic drugs and combinations of these different categories of drugs seem promising (51). The majority of large study groups have plans to conduct randomized clinical trials of standard treatment with and without target-based drugs. This area appears promising, because the ability to use rational compounds to treat lung cancer has strong biological justification.
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FOOTNOTES |
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+ For reprints and all correspondence: Nagahiro Saijo, Medical Oncology Division, National Cancer Center Hospital, 1-1 Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045
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REFERENCES |
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TOPABSTRACTINTRODUCTIONCISPLATIN VERSUS CISPLATIN +...NOVEL AGENT + CISPLATIN...NOVEL AGENT + CISPLATIN...NOVEL AGENTS + CARBOPLATIN...REMAINING ISSUES AFFECTING...REFERENCES |
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1 Non-small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomized clinical trials. Br Med J 1995;311:899–909.
2 Anderson H, Hopwood P, Stephans RJ, Thatcher N, Cottier B, Nicholson M, et al. Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer: a randomized trial with quality of life as the primary outcome. Br J Cancer 2000;83:447–53.[Web of Science][Medline]
3 Schiller JH. Chemotherapy for advanced non-small cell lung cancer. Lung Cancer, 2nd ed. Philadelphia: Lippincott Williams & Wilkins 2000;889–902.
4 Sekine I, Saijo N. Novel combination chemotherapy in the treatment of non-small cell lung cancer. Exp Opin Pharmacother 2000;1:1131–61.[Medline]
5 Klastersky J, Sculier JP, Bureau G, Libert P, Ravez P, Vandermoten G, et al. Cisplatin versus cisplatin plus etoposide in the treatment of advanced non-small-cell lung cancer. J Clin Oncol 1989;7:1087–92.[Abstract]
6 Gandara DR, Crowley J, Livingston RB, Perez EA, Taylor CW, Weiss G, et al. Evaluation of cisplatin intensity in metastatic non-small-cell lung cancer: a phase III study of the Southwest Oncology Group. J Clin Oncol 1993;11:873–8.
7 Bonomi PD, Finkelstein DM, Ruckdeschel JC, Blum H, Green MD, Mason B, et al. Combination chemotherapy versus single agents followed by combination chemotherapy in stage IV non-small cell lung cancer: a study of the Eastern Cooperative Oncology Group. J Clin Oncol 1989;7:1602–13.[Abstract]
8 Wozniak AJ, Crowley JJ, Balcerzak P, Weiss GR, Spiridonidis CH, Baker LH, et al. Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small-cell lung cancer: a Southwest Oncology Group study. J Clin Oncol 1998;16:2459–65.[Abstract]
9 Sandler AB, Nemunaitis J, Denham C, von Pawel J, Cormier Y, Gatzemeier U, et al. Phase III trial of gemcitabine plus cisplatin versus cisplatin alone in patients with locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 2000;18:122–30.
10 von Pawel J, von Roemeling R, Gatzemeier U, Boyer M, Elisson LO, Clark P, et al. Tirapazamine plus cisplatin versus cisplatin in advanced non-small-cell lung cancer: a report of the international CATAPULT I study group. J Clin Oncol 2000;18:1351–9.
11 Gatzemeier U, von Pawel J, Gottfried M, ten Velde GPM, Mattson K, DeMarinis F, et al. Phase III comparative study of high-dose cisplatin versus a combination of paclitaxel and cisplatin in patients with advanced non-small cell lung cancer. J Clin Oncol 2000;18:3390–9.
12 Bonomi P, Kim K, Fairclough D, Cella D, Kugler J, Rowinsky E, et al. Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin: results of an Eastern Cooperative Oncology Group trial. J Clin Oncol 2000;18:623–31.
13 Belani CP, Natale RB, Lee JS, Socinski M, Robert F, Waterhouse D, et al. Randomized phase III trial comparing cisplatin/etoposide versus carboplatin/paclitaxel in advanced and metastatic non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 1998;17:abstr 1751.
14 Giaccone G, Splinter TAW, Debruyne C, Khot GS, Lianes P, van Zandwijk N, et al. Randomized study of paclitaxel–cisplatin versus cisplatin–teniposide in patients with advanced non-small-cell lung cancer. The European Organization for Research and Treatment of Cancer Lung Cancer Cooperative Group. J Clin Oncol 1998;16:2133–41.[Abstract]
15 Cardenal F, Lopez-Cabrerizo MP, Anton A, Alberola V, Massuti B, Carrato A, et al. Randomized phase III study of gemcitabine–cisplatin versus etoposide–cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 1999;17:12–8.
16 Shepherd F, Koschel G, von Pawel J, Gatzemeier N, Van Zandwiyk N, Woll P, et al. Comparison of Tirazone (Tirapazamine) and cisplatin vs. etoposide and cisplatin in advanced non-small cell lung cancer (NSCLC): final results of the international Phase III CATAPULT II Trial. World Conf Lung Cancer 2000;9:abstr 87.
17 Masuda N, Fukuoka M, Negoro S, Takada Y, Sugiura T, Ohashi Y, et al. Randomized trial comparing cisplatin and irinotecan versus cisplatin and vindesine versus irinotecan alone in advanced non-small cell lung cancer, a multicenter phase III study. Proc Am Soc Clin Oncol 1999;18:abstr 1774.
18 Niho S, Nagao K, Nishiwaki Y, Yokoyama A, Saijo N, Ohashi Y, et al. Randomized multicenter phase III trial of irinotecan and cisplatin versus cisplatin and vindesine in patients with advanced non-small cell lung cancer. Proc Am Soc Clin Oncol 1999;18:abstr 1897.
19 Crino L, Scagliotti GV, Ricci S, DeMarinis F, Rinaldi M, Gridelli C, et al. Gemcitabine and cisplatin versus mitomycin, ifosfamide and cisplatin in advanced non-small-cell lung cancer: a randomized phase III study of the Italian Lung Cancer Project. J Clin Oncol 1999;17:3522–30.
20 Le Chevalier T, Brisgand D, Douillard JY, Pujol JL, Alberola V, Monnier A, et al. Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: results of a European multicenter trial including 612 patients. J Clin Oncol 1994;12:360–7.[Abstract]
21 Martoni A, Guaraldi M, Piana E, Strocchi E, Petralia A, Busutti L, et al. Multicenter randomized clinical trial on high-dose epirubicin plus cis-platinum versus vinorelbine plus cis-platinum in advanced non small cell lung cancer. Lung Cancer 1998;22:31–8.[Web of Science][Medline]
22 Galetta D, Gebbia V, Riccardi F, Borsellino N, Gridelli C, Testa A, et al. A randomized phase III trial of the Southern Italy Oncology Group (G.O.I.M.) of mitomycin C plus vindesine and cisplatin (MVP regimen) versus vinorelbine plus cisplatin (PV regimen) in stage III–IV non small cell lung cancer. World Conf Lung Cancer 2000;9:abstr 63.
23 Kawahara M, Furuse Y, Nishiwaki Y, Horai N, Saijo N, Hasegawa Y, et al. Randomized study of vinorelbine (VRB) or vindesine (VDS) with cisplatin (P) and mitomycin (M) as induction chemotherapy in stage IIIB or IV non-small cell lung cancer (NSCLC) – final results. Proc Am Soc Clin Oncol 2000;19:abstr 1914.
24 Gatzemeier U, Rosell R, Betticher D, Keppler U, Macha HN, Pirker R, et al. Randomized pan-European trial comparing paclitaxel/carboplatin versus paclitaxel/cisplatin in advanced non-small-cell lung cancer. Eur J Cancer 1999;35(suppl 4):246.
25 Kelly K, Crowley J, Bunn PA, Livingston RB, Gandara DR. A randomized phase III trial of paclitaxel plus carboplatin versus vinorelbine plus cisplatin in untreated advanced non-small-cell lung cancer. A Southwest Oncology Group Trial. Proc Am Soc Clin Oncol 1999;18:abstr 1777.
26 Schiller JH, Harrington D, Sandler A, Belani C, Langer C, Krook J, et al. A randomized phase III trial of four chemotherapy regimens in advanced non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 2000;19:abstr 2.
27 Belani CP, Rodriguez J, von Pawel J, Pluzanska A, Gorbounova V, Millward M, et al. A multicenter, randomized phase III study of docetaxel + cisplatin (DC) vs docetaxel + carboplatin (DCb) vs vinorelbine + cisplatin (VC) in chemotherapy-naïve patients (Pts) with advanced and metastatic non-small cell lung cancer (NSCLC). World Conf Lung Cancer 2000;9:abstr 195.
28 Comella P, Frasci G, Panza N, Manzione L, De Cataldis G, Cioffi R, et al. Randomized trial comparing cisplatin, gemcitabine and vinorelbine with either cisplatin and gemcitabine or cisplatin and vinorelbine in advanced non-small-cell lung cancer: interim analysis of a phase III trial of the Southern Italy Cooperative Oncology Group. J Clin Oncol 2000;18:1451–7.
29 Comella G, Comella P, Frasci G, Panza N, Nicolella P, Maiorino L, et al. Cisplatin–gemcitabine, vs. cisplatin–gemcitabine–vinorelbine, vs. cisplatin–gemcitabine–paclitaxel in advanced non-small-cell lung cancer. First-stage analysis of a Southern Italy Cooperative Oncology Group (SICOG) phase III trial. Proc Am Soc Clin Oncol 2000;19:abstr 1933.
30 Akerley W, Herndon J, Egorin MJ, Lyss A, Kindler H, Savarese D, et al. CALGB 9731: phase II trial of weekly paclitaxel for advanced non-small cell lung cancer. Proc Am Soc Clin Oncol 1999;18:abstr 1783.
31 Akerley W, Herndon J, Turrisi A, Graziano S, Williams T, Sikov W, et al. Induction chemotherapy with paclitaxel and carboplatin followed by concurrent thoracic radiation and weekly PC for patients unresectable stage III NSCLC: preliminary analysis of a phase II trial by the Cancer and Leukemia Group B. Proc Am Soc Clin Oncol 2000;19:abstr 1915.
32 Murakami H, Kubota K, Ohe Y, Watanabe H, Sawada M, Akiyama Y, et al. Phase I study of weekly docetaxel (DTX) and carboplatin (CBDCA) with concurrent thoracic radiotherapy (TRT) for stage III non-small cell lung cancer (NSCLC). World Conf Lung Cancer 2000;9:abstr 367.
33 Isokangas OP, Knuuttila A, Halme M, Mantyla M, Lindstrom I, Nikkanen V, et al. Phase II study of vinorelbine and gemcitabine for inoperable stage IIIB–IV non-small-cell lung cancer. Ann Oncol 1999;10:1059–63.
34 Miller VA, Krug LM, Ng KK, Pizzo B, Perez W, Heelan RT, et al. Phase II trial of docetaxel and vinorelbine in patients with advanced non-small cell lung cancer. J Clin Oncol 2000;18:1346–50.
35 Giaccone G, Smit E, Laan D, Splinter T, van Meerbeeck J, Postmus P, et al. Phase I/II study of paclitaxel and gemcitabine in advanced non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 1998;17:abstr 1869.
36 Kosmidis PA, Bacoyiannis N, Mylonakis N, Demopoulos MA, Dimitriadis K, Kalofonos HP, et al. A randomized phase III trial of paclitaxel plus carboplatin versus paclitaxel plus gemcitabine in advanced non-small cell lung cancer (NSCLC): a preliminary analysis. Proc Am Soc Clin Oncol 2000;19:abstr 1908.
37 Georgoulias V, Papadakis E, Alexopoulos A, Stavrinidis E, Bania E, Rapti A, et al. Docetaxel plus cisplatin versus docetaxel plus gemcitabine chemotherapy in advanced non-small cell lung cancer: a preliminary analysis of a multicenter randomized phase II trial. Proc Am Soc Clin Oncol 1999;18:abstr 1778.
38 Takeda K, Yamamoto N, Negoro S, Nakagawa K, Matsui K, Kawahara M, et al. Randomized phase II study of docetaxel (DOC) plus cisplatin (CDDP) versus DOC plus irinotecan in advanced non-small-cell lung cancer (NSCLC); a West Japan Thoracic Oncology Group (WJTOG) study. Proc Am Soc Clin Oncol 2000;19:abstr 1944.
39 Langer C, Manola P, Bernardo P, Bonomi P, Kugler A, Johnson D, et al. Advanced age alone does not compromise outcome in fit non-small cell lung cancer (NSCLC) patients (Pts) receiving platinum (DDP)-based therapy (TX): implications of ECOG 5592. Proc Am Soc Clin Oncol 2000;19:abstr 1912.
40 The Elderly Lung Cancer Vinorelbine Italian Study Group. Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small-cell lung cancer. J Natl Cancer Inst 1999;91:66–72.
41 Frasci G, Lorusso V, Panza N, Comella P, De Cataldis G, Micillo E, et al. Gemcitabine + vinorelbine yields better survival than vinorelbine alone in elderly non-small cell lung cancer patients. Final analysis of a Southern Italy Cooperative Oncology Group phase III trial. Proc Am Soc Clin Oncol 2000;19:abstr 1895.
42 Feliu J, Gomez LL, Madronal C, Espinosa E, Espinosa J, Giron CG, et al. Gemcitabine plus vinorelbine in non-small cell lung carcinoma patients age 70 years or older or patients who cannot receive cisplatin. Cancer 1999;86:1463–9.[Web of Science][Medline]
43 Ohe Y, Niho S, Kakinuma R, Kubota K, Matsumoto T, Ohmatsu H, et al. Lower recommended dose but not diminished efficacy obtained in elderly patients age 75 years or older in phase I study of cisplatin and docetaxel administered by three consecutive weekly infusions for advanced non-small cell lung cancer. World Conf Lung Cancer 2000;9:abstr 199.
44 Sekine I, Fukuda H, Kunitoh H, Saijo N. Cancer chemotherapy in the elderly. Jpn J Clin Oncol 1998;28:463–73.
45 Nakamura Y, Sekine I, Furuse K, Saijo N. Retrospective comparison of toxicity and efficacy in phase II trials of 3-h infusions of paclitaxel for patients 70 years of age or older and patients under 70 years of age. Cancer Chemother Pharmacol 2000;46:114–8.[Web of Science][Medline]
46 Shepherd FA, Dancey J, Ramlau R, Mattson K, Gralla R, O’Rourke M, et al. Prospective randomized trial of docetaxel versus best supportive care in patients with non-small-cell lung cancer previously treated with platinum-based chemotherapy. J Clin Oncol 2000;18:2095–103.
47 Fossella FV, DeVore R, Kerr RN, Crawford J, Natale RR, Dunphy F, et al. Randomized phase III trial of docetaxel versus vinorelbine or ifosfamide in patients with advanced non-small-cell lung cancer previously treated with platinum-containing chemotherapy regimens. J Clin Oncol 2000;18:2354–62.
48 Crino L, Mosconi AM, Scagliotti G, De Marinis F, Dawish S, Calandri C, et al. Salvage therapy with gemcitabine (GEM) in pretreated, advanced non-small cell lung cancer (NSCLC). Proc Am Soc Clin Oncol 1997;16:abstr 1603.
49 Murphy WK, Winn RJ, Huber M, Fossella FV, Goldberg D, Presant CA, et al. Phase II study of Taxol (T) in patients (PT) with non-small cell lung cancer (NSCLC) who have failed platinum (P) containing chemotherapy (CTX). Proc Am Soc Clin Oncol 1994;13:abstr 1224.
50 Kusaba H, Nakamura Y, Kunitoh H, Sekine I, Kubota K, Tamura T, et al. A phase II trial of low-dose docetaxel (DCT) 60 mg/m2 in platinum-pretreated advanced non-small cell lung cancer (NSCLC). World Conf Lung Cancer 2000;9:abstr 77.
51 DeVore RF, Fehrenbacher L, Herbst RS, Langer CJ, Kelly K, Gaudreault J, et al. A randomized phase II trial comparing Rhumab VEGF (recombinant humanized monoclonal antibody to vascular endothelial cell growth factor) plus carboplatin/paclitaxel (CP) to CP alone in patients with stage IIIB/IV NSCLC. Proc Am Soc Clin Oncol 2000;19:abstr 1896.
Received November 15, 2000; accepted April 10, 2001.
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