Induction chemotherapy before surgery for early-stage lung cancer: A novel approach

Pisters, Katherine M.W.; Ginsberg, Robert J.; Giroux, Dorothy J.; Putnam, Joe B.; Kris, Mark G.; Johnson, David H.; Roberts, John R.; Mault, James R.; Crowley, John; Bunn, Paul A.

doi:10.1016/s0022-5223(00)70120-6

Cited by 229 publications

(70 citation statements)

References 19 publications

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“…20 It is also reported that induction chemotherapy with other new drugs produces a high response rate in early stage NSCLC. 21 Therefore, the subjects of our study were limited to pathological Stage I or II NSCLC patients. A quantitative real-time RT-PCR assay is able to determine mRNA levels from nanogram amounts of total RNA, 22 thus, it is possible to measure TS mRNA levels in biopsy specimens obtained with a bronchofiberscope or needle biopsy.…”

Section: Discussionmentioning

confidence: 99%

New prognostic indicator for non‐small‐cell lung cancer, quantitation of thymidylate synthase by real‐time reverse transcription polymerase chain reaction

Shintani¹,

Ohta²,

Hirabayashi³

et al. 2003

Intl Journal of Cancer

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Thymidylate synthase (TS) is an enzyme that catalyzes an important DNA biosynthesis process. The gene expression of TS has not been reported in non-small-cell lung cancer (NSCLC) patients. To clarify the correlation between TS mRNA levels and clinicopathological features of NSCLC, we examined 70 Stage I and II NSCLC patients for intra-tumoral expression of TS using TaqMan reverse transcription polymerase chain reaction (RT-PCR) assay and immunohistochemistry methods. We also investigated the TS promoter 28 bp polymorphism in 48 cancer tissues using PCR amplification of genomic DNA. Lung cancer tissue showed higher TS mRNA levels than normal lung tissue (Mann-Whitney U-tests; p ‫؍‬ 0.0020). Further, TS mRNA expression was correlated with immunohistochemical TS expression (p ‫؍‬ 0.029). We obtained 2 different DNA fragments, which indicated triple-repeat (3R) and double-repeat (2R) type alleles. Cancer tissues with the 3R/3R genotype showed significantly higher TS mRNA levels as compared to those with other genotypes (p ‫؍‬ 0.0019). The TS genotype was also correlated with immunohistochemical TS expression ( 2 test; p ‫؍‬ 0.0079). The disease-free survival of the low TS mRNA level group was significantly better than those with high TS mRNA levels (log-rank test; p ‫؍‬ 0.010), however, there were no significant differences found by immunohistochemical evaluation (p ‫؍‬ 0.34) or TS genotype analysis (p ‫؍‬ 0.11). A multivariate analysis revealed that high TS mRNA levels independently contributed to disease-free survival. The quantitation of TS mRNA levels is clinically more sensitive and useful for determining the prognosis of Stage I and II NSCLC patients than an immunohistochemical evaluation. © 2003 Wiley-Liss, Inc. Key words: thymidylate synthase; non-small-cell lung cancer; disease-free survival; real-time RT-PCR; DNA polymorphism; immunohistochemistryThymidylate synthase (TS) is an enzyme that catalyzes the methylation of fluorodeoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), which is an important process for DNA biosynthesis. 1-3 Recent studies have demonstrated that the prognosis of cancer patients is significantly related to TS intra-tumoral immunohistochemical expression and mRNA levels. 4 -6 In non-small-cell lung cancer (NSCLC) patients, TS expression shown by immunohistochemical staining is considered to be an important prognostic indicator to determine survival, 6 however, TS mRNA levels have not been reported. To clarify the correlation between TS mRNA levels and clinicopathological features of NSCLC, we examined Stage I and II NSCLC patients for intra-tumoral expression of TS using real-time reverse transcription polymerase chain reaction (RT-PCR) assay and immunohistochemical methods.The TS gene has a unique tandem repeated sequence in the 5Ј-untranslated region and the number of repeats has been found to be polymorphic. 7 The presence of the triple vs. double 28 base pair (bp)-sized repeat was shown to enhance gene expression in in vitro and in vivo studies. 7,8 We investi...

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Section: Discussionmentioning

confidence: 99%

New prognostic indicator for non‐small‐cell lung cancer, quantitation of thymidylate synthase by real‐time reverse transcription polymerase chain reaction

Shintani¹,

Ohta²,

Hirabayashi³

et al. 2003

Intl Journal of Cancer

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“…Assuming DFS rates at 1 year of 70 and 80%, 40 patients per arm were required to correctly select the arm that is not inferior with the probability of 84.9%. The 'minimal' DFS rate of 70% was assumed with the prior report from North America, in which the 1-and 2-year survival rates were reported to be 85 and 56%, respectively (Pisters et al, 2000). The assumption was rough and might well be inaccurate, for no DFS data were available from the literature.…”

Section: Statistical Considerationsmentioning

confidence: 99%

“…Recent trials of preoperative platinum-based chemotherapy have reported promising results in c-stage IB/II NSCLC (Pisters et al, 2000;Depierre et al, 2002;Rosell et al, 2002). One advantage of the preoperative chemotherapy is better tolerability and compliance.…”

mentioning

confidence: 99%

A randomised phase II trial of preoperative chemotherapy of cisplatin–docetaxel or docetaxel alone for clinical stage IB/II non-small-cell lung cancer: results of a Japan Clinical Oncology Group trial (JCOG 0204)

et al. 2008

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Preoperative chemotherapy is a promising strategy in patients with early-stage resectable non-small-cell lung cancer (NSCLC); optimal chemotherapy remains unclear. Clinical (c-) stage IB/II NSCLC patients were randomised to receive either two cycles of docetaxel (D) -cisplatin (P) combination chemotherapy (D 60 mg m À2 and P 80 mg m À2 on day 1) every 3 -4 weeks or three cycles of D monotherapy (70 mg m À2 ) every 3weeks. Thoracotomy was performed 4 -5 weeks (DP) or 3 -4 weeks (D) after chemotherapy. The primary end point was 1-year disease-free survival (DFS). From October 2002 to November 2003, 80 patients were randomised. Chemotherapy toxicities were mainly haematologic and well tolerated. There were two early postoperative deaths with DP (one intraoperative bleeding and one empyema). Pathologic complete response was observed in two DP patients. Docetaxel -cisplatin was superior to D in terms of response rate (45 vs 15%) and complete resection rate (95 vs 87%). Both DFS and overall survival were better in DP. Disease-free survival at 1, 2 and 4 years were 78, 65 and 57% with DP, and were 62, 44 and 36% with D, respectively. Preoperative DP was associated with encouraging resection rate and DFS data, and phase III trials for c-stage IB/II NSCLC are warranted.

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“…Although the strongest rationale for the use of the trimodality therapy stems from the promising results of clinical phase II data, upfront systemic chemotherapy offers several practical as well as theoretical advantages (Pisters et al, 2000). Early introduction of systemic therapy may be expected to lead to early control of micrometastases.…”

Section: Rationales For Trimodality Therapymentioning

confidence: 99%

“…However, the compliance rate for this strategy was reported to be poor (Pisters et al, 2000;Rusch et al, 2001). In addition, some deaths related to drug toxicity have also been reported during the consolidation phase (Albain et al, 2005), prompting further questioning of its benefits.…”

Section: Toxicity Of the Chemoradiotherapymentioning

confidence: 99%

How to evaluate the risk/benefit of trimodality therapy in locally advanced non-small-cell lung cancer

Kunitoh¹,

Suzuki²

2007

Br J Cancer

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The trimodality approach represented by concurrent chemoradiotherapy followed by surgical resection is a highly effective, but potentially toxic therapy for locally advanced non-small-cell lung cancer (NSCLC). In this review, we discuss the current status of this therapy in patients with mediastinal node-positive (N2) stage III NSCLC or superior sulcus tumor, and present an overview of the principles for optimisation of the risk/benefit. Numerous clinical questions remain, and enrolment of patients into well-designed clinical trials should be encouraged.

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Induction chemotherapy before surgery for early-stage lung cancer: A novel approach

Cited by 229 publications

References 19 publications

New prognostic indicator for non‐small‐cell lung cancer, quantitation of thymidylate synthase by real‐time reverse transcription polymerase chain reaction

New prognostic indicator for non‐small‐cell lung cancer, quantitation of thymidylate synthase by real‐time reverse transcription polymerase chain reaction

A randomised phase II trial of preoperative chemotherapy of cisplatin–docetaxel or docetaxel alone for clinical stage IB/II non-small-cell lung cancer: results of a Japan Clinical Oncology Group trial (JCOG 0204)

How to evaluate the risk/benefit of trimodality therapy in locally advanced non-small-cell lung cancer

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