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Treatment of Patients with Advanced Non–Small Cell <strong>Lung</strong> <strong>Cancer</strong> 167 ever, third-generation single agents are probably inferior to the same agent combined with a platinum, notwithstanding the equivalence seen in the Depierre study (Depierre et al, 1994; Le Chevalier et al, 1994; Komiya et al, 2000). Therefore, third-generation monotherapy appears to be superior to BSC, perhaps equivalent to a platinum–early-generation doublet but likely inferior to platinum–third-generation doublets. Studies have shown that doublets consisting of vinorelbine, gemcitabine, or tirapazamine plus cisplatin are associated with longer survival times than single-agent cisplatin (Wozniak et al, 1998; Gatzemeier et al, 2000; Sandler et al, 2000; von Pawel et al, 2000) (Table 9– 4). Although the paclitaxel combination was not associated with improved survival in the Gatzemeier study, it was relatively well tolerated as compared with highdose single-agent cisplatin. Doublets composed of platinum compounds plus third-generation agents are generally better tolerated than older cisplatin-containing combinations and tend to result in modest improvement in survival (Belani et al, 1998; Giaccone et al, 1998; Martoni et al, 1998; Cardenal et al, 1999; Crino et al, 1999; Bonomi et al, 2000; Komiya et al, 2000; Takiguchi et al, 2000; Kunitoh et al, 2001; Le Chevalier et al, 2001) (Table 9–5). Of the 11 trials listed in Table 9–5, two showed significant improvement in survival with third-generation doublets, and 3 others showed a trend towards improvement in survival. These 5 trials used vinorelbine, paclitaxel, gemcitabine, docetaxel, and irinotecan. In addition, 4 other trials showed better tolerability if not an obvious survival advantage with third-generation regimens compared to older regimens. One trial showed neither improved survival nor improved tolerability (Belani et al, 1998), and one trial showed a trend toward inferior survival (Danson et al, 2001). Therefore, 9 of 11 trials showed at least a trend toward better survival or tolerability with the use of third-generation–platinum doublets. Though few of the initial phase III trials investigating combinations of platinum compounds and third-generation agents used carboplatin, this drug has become a standard part of the armamentarium against advanced NSCLC. Carboplatin is a cisplatin analogue but differs from cisplatin in its side effect profile. The primary side effect of carboplatin is myelosuppression, and carboplatin has lesser ototoxicity, renal toxicity, and neurotoxicity than cisplatin. In an early 5-arm randomized trial, carboplatin produced the best median survival time (Bonomi et al, 1989). At least 5 trials have compared different platinum compound–thirdgeneration-agent doublets (Schiller et al, 2000; Fossella, 2001; Kelly et al, 2001a; Rodriguez et al, 2001; Scagliotti et al, 2001; Van Meerbeeck et al, 2001) (Table 9–6). Unlike earlier phase III trials in which third-generation agents were combined with cisplatin, many of the trials shown in Table 9–6 replaced cisplatin with carboplatin. With the exception of the TAX 326 trial, the doublets examined in each study yielded similar response, toxicity, and overall survival outcomes.
Table 9–4. Third-Generation Agents plus Platinum versus Single-Agent Platinum Compounds Median 1-Year Side Effects Study and No. of Response Survival Survival P for Quality of Worse Than with Treatment Regimen Patients Rate Time Rate Survival Life Other Regimen Wozniak (1998) Cisplatin 209 12% 6 months 20% NR Cisplatin vinorelbine 206 26% 8 months 36% .0018 Neutropenia (P .0002) Sandler (2000) Cisplatin 262 11.1% 7.6 months 28% NR Neutropenia and thrombocytopenia Cisplatin gemcitabine 260 30.4% 9.1 months 39% .004 (P.0001) Gatzemeier (2000) Cisplatin (100 mg/m 2 ) 207 17% 8.6 months 36% Same Ototoxicity, N/V, nephrotoxicity Cisplatin 80 mg/m 2 207 26% 8.1 months 30% .862 paclitaxel 175 mg/m 2 (P .028) Von Pawel (2000) Cisplatin 219 13.7% 6.4 months 23% NR Cisplatin tirapazamine 218 27.5% 8.4 months 34% .0078 (P .001) NR indicates not reported; N/V, nausea and vomiting. 168 R. Zinner
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Lung Cancer Frank V. Fossella, MD R
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Frank V. Fossella, MD Department of
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vi Foreword possible. Since the res
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x Contents Chapter 7 Surgical Treat
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xii Contributors Joe B. Putnam, Jr.
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2 J.B. Putnam, Jr., F.V. Fossella,
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26 F.V. Fossella common sites of lu
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28 F.V. Fossella history and physic
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30 F.V. Fossella Computed Tomograph
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32 F.V. Fossella Pulmonary Function
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34 F.V. Fossella The use of flexibl
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36 R.F. Munden and J.J. Erasmus hav
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38 R.F. Munden and J.J. Erasmus che
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40 R.F. Munden and J.J. Erasmus tha
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42 R.F. Munden and J.J. Erasmus (Gu
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44 R.F. Munden and J.J. Erasmus A B
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46 R.F. Munden and J.J. Erasmus in
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48 R.F. Munden and J.J. Erasmus Pat
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50 R.F. Munden and J.J. Erasmus D C
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52 R.F. Munden and J.J. Erasmus A B
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54 R.F. Munden and J.J. Erasmus Bol
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56 R.F. Munden and J.J. Erasmus Swe
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58 P. Tamboli and J.Y. Ro Chapter O
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60 P. Tamboli and J.Y. Ro Figure 4-
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62 P. Tamboli and J.Y. Ro Postopera
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64 P. Tamboli and J.Y. Ro Table 4-1
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66 P. Tamboli and J.Y. Ro Atypical
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68 P. Tamboli and J.Y. Ro Diffuse I
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70 P. Tamboli and J.Y. Ro noma. Cig
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72 P. Tamboli and J.Y. Ro Figure 4-
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74 P. Tamboli and J.Y. Ro alone. BA
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76 P. Tamboli and J.Y. Ro Other Mal
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78 P. Tamboli and J.Y. Ro Electron
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80 P. Tamboli and J.Y. Ro Niho S, Y
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82 Y. De Jesus and G.L. Walsh Chapt
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84 Y. De Jesus and G.L. Walsh Figur
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86 Y. De Jesus and G.L. Walsh guide
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88 Y. De Jesus and G.L. Walsh with
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Figure 5-2. Patient “pathway to r
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94 Y. De Jesus and G.L. Walsh Recov
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98 Y. De Jesus and G.L. Walsh KEY P
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100 Y. De Jesus and G.L. Walsh Jenn
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102 W.R. Smythe nation for these su
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104 W.R. Smythe patient reports of
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106 W.R. Smythe bar or limited lung
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108 W.R. Smythe hospitals for 149 p
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110 W.R. Smythe Figure 6-1. Postsur
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112 W.R. Smythe nant neoplasms has
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114 W.R. Smythe Future Directions F
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Page 131 and 132: 7 SURGICAL TREATMENT OF LOCALLY ADV
Page 133 and 134: 120 S.G. Swisher Treatment Options
Page 135 and 136: 122 S.G. Swisher Initial Assessment
Page 137 and 138: 124 S.G. Swisher Figure 7-1. Region
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Page 141 and 142: 128 S.G. Swisher upper paratracheal
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Page 147 and 148: 134 S.G. Swisher Pancoast tumors th
Page 149 and 150: 136 S.G. Swisher A B Figure 7-2. Do
Page 151 and 152: 138 S.G. Swisher a combination of t
Page 153 and 154: 140 S.G. Swisher Dartevelle PG, Cha
Page 155 and 156: 8 NONSURGICAL TREATMENT OF EARLY-ST
Page 157 and 158: 144 R. Komaki morbid conditions pre
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Page 161 and 162: 148 R. Komaki Around 1998, by using
Page 163 and 164: 150 R. Komaki Table 8-5. Survival a
Page 165 and 166: 152 R. Komaki A total of 610 patien
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Page 171 and 172: 9 TREATMENT OF PATIENTS WITH ADVANC
Page 173 and 174: 160 R. Zinner chemotherapy, in pati
Page 175 and 176: Table 9-1. Chemotherapy in Older Pa
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Page 201 and 202: 188 R. Komaki Age is not a signific
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Page 205 and 206: Table 10-1. Complete Response Rates
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Page 219 and 220: 206 R. Komaki Wagner H, Kim K, John
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218 G.R. Blumenschein, Jr. new cyto
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12 PALLIATIVE CARE IN PATIENTS WITH
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222 J.B. Putnam, Jr. therapy. Patie
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224 J.B. Putnam, Jr. tion—includi
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226 J.B. Putnam, Jr. rates were 47%
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228 J.B. Putnam, Jr. Dyspnea The ma
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230 J.B. Putnam, Jr. Small-bore cat
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232 J.B. Putnam, Jr. A B Figure 12-
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234 J.B. Putnam, Jr. C D Figure 12-
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236 J.B. Putnam, Jr. B Figure 12-3.
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238 J.B. Putnam, Jr. KEY PRACTICE P
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240 J.B. Putnam, Jr. Rendina EA, De
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242 A.A. Vaporciyan, J.F. Kelly, an
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14 PREVENTION AND EARLY DETECTION O
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258 E.S. Kim and F.R. Khuri A secon
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260 E.S. Kim and F.R. Khuri Smoking
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262 E.S. Kim and F.R. Khuri Reversa
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264 E.S. Kim and F.R. Khuri yet to
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266 E.S. Kim and F.R. Khuri nation
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268 E.S. Kim and F.R. Khuri Methodo
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270 E.S. Kim and F.R. Khuri have be
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272 E.S. Kim and F.R. Khuri the tre
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274 E.S. Kim and F.R. Khuri changes
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276 E.S. Kim and F.R. Khuri KEY PRA
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278 E.S. Kim and F.R. Khuri Hong WK
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15 MOLECULAR EVENTS IN LUNG CANCER
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282 W.N. Hittelman, J.M. Kurie, and
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300 Index Anterior spinal column re
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302 Index Cardiac murmurs, 104 Card
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304 Index Diagnosis. See also under
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306 Index Growth. See Tumor growth
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308 Index Magnetic resonance (MR) i
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310 Index p16 gene, 285 p19 arf gen
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312 Index Pulmonary resection (cont
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314 Index Squamous metaplasia, 263-
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316 Index Vitamin A, 262 Vocal cord
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