Concurrent chemotherapy (carboplatin, paclitaxel, etoposide) and involved-field radiotherapy in limited stage small cell lung cancer: a Dutch multicenter phase II study

Baas, Paul; Belderbos, J.; Senan, Suresh; Kwa, H.B.; Bochove, Aart van; Tinteren, Harm van; Burgers, Jacobus A.; Meerbeeck, Jan P. van

doi:10.1038/sj.bjc.6602979

Cited by 85 publications

(44 citation statements)

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“…This rate is in accordance with our previous study (11%) which had the same up-front PCI treatment design [12]. In most other studies, the rate of brain recurrence was higher (30-40%) [11,[20][21][22]. In these studies, PCI was given to the patients with at least partial response after the end of the RCHT.…”

Section: Discussionsupporting

confidence: 90%

Is there a place for low-dose chest and prophylactic brain irradiation in limited-disease small cell lung cancer

et al. 2008

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The aim of the study is to evaluate the outcome of low-dose bifractionated up-front radiotherapy (RT) followed by chemotherapy (CHT) in limited-disease small cell lung cancer (LD-SCLC). From December 1999 to February 2002, 20 LD-SCLC consecutive patients were treated by initial involved-field thoracic irradiation of 2 Gy twice daily to a total dose of 20 Gy, and concomitant prophylactic cranial irradiation (PCI) of 1.8 Gy twice daily to a total dose of 18 Gy followed 3 days later by 4-6 cycles of CHT with cisplatin and etoposide. Median follow-up was 66 months (52-77). There were no Grade 3-4 esophagitis or pneumonitis. Response rate was 90%, 45% of the patients showing a complete and 45% a partial response. Median time to first event was 13 months. Forty percent showed local infield recurrence, while 55% presented distant metastasis, 4 of them in the brain. Median survival time was 28 months. The Kaplan-Meier 1-, 3-, and 5-years survival rates were 95%, 35%, and 21%, respectively. Salvage RT was applied for local recurrence in 7 patients and for distant metastasis in 7 patients. The rate of brain recurrence with up-front low-dose PCI is favorable and should be further evaluated. Although the response and survival rates are promising, the high number of local recurrences indicates that the irradiation dose is insufficient for patients whose disease can be encompassed within a radical radiation portal.

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Section: Discussionsupporting

confidence: 90%

Is there a place for low-dose chest and prophylactic brain irradiation in limited-disease small cell lung cancer

et al. 2008

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“…Several phase II trials have investigated the role of carboplatin and etoposide with concurrent TRT [53,54], and a retrospective review has revealed outcomes similar to those with cisplatin-based therapy [55]. However, phase III data comparing the efficacy of carboplatin with that of cisplatin in LS-SCLC are lacking and phase III data from carboplatin-based chemoradiotherapy are limited.…”

Section: Chemotherapy and Targeted Agents In Ls-sclcmentioning

confidence: 99%

Limited-Stage Small Cell Lung Cancer: Current Chemoradiotherapy Treatment Paradigms

Stinchcombe

Gore

2010

The Oncologist

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In the U.S., the prevalence of small cell lung cancer (SCLC) is declining, probably reflecting the decreasing prevalence of tobacco use. However, a significant number of patients will receive a diagnosis of SCLC, and approximately 40% of patients with SCLC will have limited-stage (LS) disease, which is potentially curable with the combination of chemotherapy and radiation therapy. The standard therapy for LS-SCLC is concurrent chemoradiotherapy, and the 5-year survival rate observed in clinical trials is approximately 25%. The standard chemotherapy remains cisplatin and etoposide, but carboplatin is frequently used in patients who cannot tolerate or have a contraindication to cisplatin. Substantial improvements in survival have been made through improvements in radiation therapy. Concurrent chemoradiotherapy is the preferred therapy for patients who are appropriate candidates. The optimal timing of concurrent chemoradiotherapy is during the first or second cycle, based on data from meta-analyses. The optimal radiation schedule and dose remain topics of debate, but 1.5 Gy twice daily to a total of 45 Gy and 1.8 -2.0 Gy daily to a total dose of 60 -70 Gy are commonly used treatments. For patients who obtain a near complete or complete response, prophylactic cranial radiation reduces the incidence of brain metastases and improves overall survival. The ongoing Radiation Therapy Oncology Group and Cancer and Leukemia Group B and the European and Canadian phase III trials will investigate different radiation treatment paradigms for patients with LS-SCLC, and completion of these trials is critical.

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“…We have updated our analysis of failure patterns in patients with limited-stage SCLC who were treated in our phase II study of involved-field irradiation during the second and third cycles of carboplatin, paclitaxel and etoposide (Baas et al, 2006). Of the 36 patients, isolated out-of-field nodal failures were only seen in two patients, one of whom developed an ipsilateral supraclavicular nodal recurrence after 10 months and the other developed a recurrence in the left hilar region after 18 months follow-up.…”

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Reply: Patterns of nodal recurrence after omission of elective nodal irradiation for limited-stage small-cell lung cancer

2007

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We thank Dr Chun-Ru Chien et al for their interest in our recent study and for their remarks concerning the safety of using involvedfield irradiation in treating limited-stage small-cell lung cancer (SCLC). We have updated our analysis of failure patterns in patients with limited-stage SCLC who were treated in our phase II study of involved-field irradiation during the second and third cycles of carboplatin, paclitaxel and etoposide (Baas et al, 2006). Of the 36 patients, isolated out-of-field nodal failures were only seen in two patients, one of whom developed an ipsilateral supraclavicular nodal recurrence after 10 months and the other developed a recurrence in the left hilar region after 18 months follow-up. In-field recurrences were observed in nine patients, and this was the sole site of recurrence in four patients. One patient developed a large-cell carcinoma within the treatment field 5.2 years after the diagnosis of SCLC. In two other patients, simultaneous recurrences manifested both within-and out-of-field regional nodes. A further two patients presented with a simultaneous local recurrence and distant metastases.Recently, De Ruysscher et al (2006)published their prospective evaluation of patterns of recurrence in twenty-seven limited-stage SCLC patients irradiated without elective nodal fields (without use of 18-fluoro-2-deoxyglucose positron-emission tomography (18FDG-PET) scans). Three of their 27 patients developed an isolated nodal failure in the ipsilateral supraclavicular region. They concluded that the omission of elective nodal irradiation in SCLC patients should be performed in the context of trials only. It could be argued that the dose used in our trial of 45 Gy in 5 weeks was too low, and local recurrences occurred before nodal failures became evident. De Ruysscher prescribed a more intense radiotherapy schedule of 45 Gy given in 3 weeks (twice daily irradiation with a 6 -8 h interval). It is unclear as to why the supraclavicular region was prone to isolated recurrences. In general, this area is difficult to assess on the computed tomography (CT) scan of the thorax (and is often not fully accessed). A solution for this problem is to ensure an optimal contrast-enhanced CT scan, which includes the supraclavicular region. The addition of a routine ultrasound of the supraclavicular area has been shown to improve staging in both NSCLC (non-small-cell lungs cancer) and SCLC (Van Overhagen et al, 2004). In addition, recent literature suggests that 18FDG-PET scans could be of additional value in staging patients with limited-stage SCLC (Bradley et al, 2004;Fischer et al, 2007).A phase III trial of concurrent chemoradiotherapy without elective nodal irradiation in limited-stage SCLC, where patients will be randomised to either once daily irradiation to a dose of 66 Gy or twice daily irradiation to a dose of 45 Gy will shortly commence (Faivre-Finn, 2006). Such a trial will generate more reliable data on the safety of omitting elective nodal irradiation in this disease. Until additional data become ...

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Concurrent chemotherapy (carboplatin, paclitaxel, etoposide) and involved-field radiotherapy in limited stage small cell lung cancer: a Dutch multicenter phase II study

Cited by 85 publications

References 29 publications

Is there a place for low-dose chest and prophylactic brain irradiation in limited-disease small cell lung cancer

Is there a place for low-dose chest and prophylactic brain irradiation in limited-disease small cell lung cancer

Limited-Stage Small Cell Lung Cancer: Current Chemoradiotherapy Treatment Paradigms

Reply: Patterns of nodal recurrence after omission of elective nodal irradiation for limited-stage small-cell lung cancer

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