Radiosensitization by cytotoxic drugs. The EORTC experience by the Radiotherapy and Lung Cancer Cooperative Groups

Schaake-Koning, C.; Bogaert, Walter Van den; Dalesio, Otilia; Festen, J.; Hoogenhout, J.; Houtte, Paul Van; Kirkpatrick, A.; Koolen, Marijn; Maat, B.; Nijs, A; Renaud, Alain; Rodrigus, P.; Schuster-Uitterhoeve, L.; Sculier, Jean-Paul; Zandwijk, Nico van; Bartelink, Harry

doi:10.1016/0169-5002(94)91690-x

Cited by 34 publications

(34 citation statements)

References 11 publications

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“…These evidences, to some extent, support the results of Schaake-Koning et al: 50 the improved survival after concomitant RT-CT seems to be primarily mediated through increased local and regional control. It is probable that concomitant RT-CT promises a RT-enhancing effect on tumor volume associated with improved locoregional control, but reductions in dose intensity of CT due to increased morbidity and life threatening toxic events may not have any effects on metastasis.…”

Section: Cancer Therapysupporting

confidence: 80%

“…The principal disadvantage of the concurrent regimen is the enhancement of normal tissue toxicity, both hematologic and non-hematologic, resulting in unnecessary subject morbidity and attenuation of RT and/or CT delivery. 50 Hence, both sequential and concurrent RT-CTs have a theoretical benefit and potentially complementary activities. The present study compared the relative efficacy between the two strategies in advanced NSCLC.…”

Section: Discussionmentioning

confidence: 99%

“…It is probable that concomitant RT-CT promises a RT-enhancing effect on tumor volume associated with improved locoregional control, but reductions in dose intensity of CT due to increased morbidity and life threatening toxic events may not have any effects on metastasis. 50 Sequential arm, on the other hand, allows for early delivery of full systemic dose of CT and is thus suited to eradicate micrometastasis. 7 The objectives for the treatment of advanced NSCLC are palliative and include improvement of survival, symptom control, quality of life (QOL), and cost.…”

Section: Cancer Therapymentioning

confidence: 99%

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Chemo‐radiotherapy for advanced non‐small cell lung cancer: concurrent or sequential? It's no longer the question: a systematic review

Lee

Zhou

et al. 2010

Intl Journal of Cancer

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There has been conflicting evidence concerning the best sequence of radiotherapy (RT) and chemotherapy (CT) for advanced non-small-cell-lung-cancer (NSCLC). To investigate whether current clinical trials can clarify this schedule and offer further bases for clinical decision making, we performed a systematic review of 11 trials (2,043 patients; concurrent-1,019, sequential-1,024) that compared concurrent RT-CT with sequential arm in advanced NSCLC patients. Primary end point was overall survival (OS). Pooled median ratios (MRs) and progression-free-survival ratios (FRs) for median survival and progression-free survival (PFS) were calculated using the weighted sum of the log ratio of MR and FR of individual study. Pooled odds ratios (ORs) for the objective response rate, relapse control rate, and toxic events were calculated using the Mantel-Haenszel estimate. Results confirmed that concurrent RT-CT determined a statistically significant increase in median survival time (16.3 vs. 13.9 months; MR 5 1.17,95%CI:1.09-1.26), response rate (64.0% vs. 56.3%; OR 5 1.38,95%CI:1.10-1.72), and tumor-relapse control (OR 5 0.82,95%CI:0.69-0.97), though at the expense of increased hematological toxicity (neutropenia and thrombocytopenia) and non-hematological toxicity (nausea/vomiting, stomatitis, and esophagitis). Similar results were obtained from the sensitivity analysis of all Phase-III/trials designed to evaluate the primary end point of OS. Subgroup analysis revealed that concurrent strategy was mainly associated with improved loco-regional control (OR 5 0.68,95%CI:0.52-0.87). However, no difference in PFS is shown. While careful interpretation of our conclusions is required because of potential bias, the present study, to some extent, exhibits the superiority of the concurrent arm over the sequential in the treatment of advanced NSCLC. Further improvements will be obtained by optimizing the conditions for a concurrent regimen.Lung cancer, with its high incidence and grim prognosis, remains a major public health menace for both men and women worldwide. 1,2 Non-small-cell lung cancer (NSCLC) accounts for more than 80% of all lung tumors. 3,4 For early stage NSCLC, surgical resection continues to be the standard treatment with curative intent. 5 Unfortunately, approximately 70% of NSCLC patients are diagnosed in advanced stage of the disease (locoregionally advanced or distant metastatic disease). 3,6 Advanced NSCLC, characterized by large primary lesions and/or widespread involvement of the ipsilateral or contralateral mediastinum or supraclavicular regions, 7,8 poses a major therapeutic challenge not only due to poor response to treatment but also due to treatment related morbidities. 9 Although there is currently no official consensus on the definitive treatment of advanced NSCLC, it has been well documented that the addition of chemotherapy to radiotherapy improves survival. [10][11][12][13][14] Combined modality approaches have been studied intensively, including concurrent radio-chemotherapy (RT-CT) and sequential RT...

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Section: Cancer Therapysupporting

confidence: 80%

Section: Discussionmentioning

confidence: 99%

Section: Cancer Therapymentioning

confidence: 99%

See 1 more Smart Citation

Chemo‐radiotherapy for advanced non‐small cell lung cancer: concurrent or sequential? It's no longer the question: a systematic review

Lee

Zhou

et al. 2010

Intl Journal of Cancer

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“…Owing to the accelerated cell proliferation observed, accelerated radiotherapy should be given serious consideration to keep overall treatment time short. In further studies, concurrent chemo/radiotherapy treatment should be considered since a growing body of data show that concurrent chemo/radiotherapy improves survival in selected patients in stage III NSCLC (Schaake-Koning et al, 1994;Furuse et al, 1999;Curran et al, 2003).…”

Section: Repopulation and Tumour Doubling Timementioning

confidence: 99%

Accelerated regrowth of non-small-cell lung tumours after induction chemotherapy

2003

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Induction chemotherapy of non-small-cell lung cancer (NSCLC) stage III with gemcitabine and cisplatin for downstaging of the tumour with the aim for further treatment with ionising radiation is one of the treatments for lung cancer patients. The purpose of this study was to investigate the influence of the waiting time for radiotherapy, that is, the interval between induction chemotherapy and radiotherapy, on the rate of tumour growth for patients with NSCLC. Interval times between the end of induction chemotherapy and date of diagnostic CT, planning CT and first day of radiotherapy were determined for 23 patients with NSCLC. Increase in gross tumour volume was measured for 18 patients by measuring the dimensions of the primary tumour and lymph node metastases on the diagnostic CT after induction chemotherapy and on the CT used for radiotherapy planning. For each patient, the volume doubling time was calculated from the time interval between the two CTs and ratio of the gross volumes on planning CT and diagnostic CT. The mean time interval between end of chemotherapy and day of diagnostic CT was 16 days, and till first day of radiotherapy 80.3 (range 29 -141) days. In all, 41% of potentially curable patients became incurable in the waiting period. The ratio of gross tumour volumes of the two CTs ranged from 1.1 to 81.8 and the tumour doubling times ranged from 8.3 to 171 days, with a mean value of 46 days and median value of 29 days. This is far less than the mean doubling time of NSCLC in untreated patients found in the literature. This study shows that in the time interval between the end of induction chemotherapy and the start of radiotherapy rapid tumour progression occurs as a result of accelerated tumour cell proliferation: mean tumour doubling times are much shorter than those in not treated tumours. As a consequence, the gain obtained with induction chemotherapy with regard to volume reduction was lost in the waiting time for radiotherapy. We recommend diminishing the time interval between chemo-and radiotherapy to as short as possible.

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“…The NSCLCCG meta-analysis confirmed the survival benefit provided by giving cisplatinbased chemotherapy before radiotherapy over radiotherapy alone (Non-Small Cell Lung Cancer Collaborative Group, 1995). Although it is standard to use induction chemotherapy followed by radiotherapy, there are some arguments favouring concurrent chemoradiation using chemotherapy at systemic dosages (Eberhardt et al, 1998;Jeremic et al, 1999) or at radiosensitising dosages (Trovo et al, 1992;Schaake-Koning et al, 1994;Bardet et al, 1997;Clamon et al, 1999). These two different treatment modalities have been studied in a number of promising phase II trials but there are very limited data from positive randomised phase III trials (Schaake-Koning et al, 1994;Furuse et al, 1999).…”

Section: Combined Modality and Adjuvant Therapymentioning

confidence: 99%

Platinum drugs in the treatment of non-small-cell lung cancer

Cosaert

Quoix

2002

Br J Cancer

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The use of chemotherapy is considered standard therapy in patients with locally advanced non-small-cell lung cancer that cannot be treated with radiotherapy and in those with metastatic non-small-cell lung cancer and good performance status. This approach is also accepted in patients with earlier stage disease, when combined with radiotherapy in those with nonresectable locally advanced disease, or in the preoperative setting. Randomised clinical studies and meta-analyses of the literature have confirmed the beneficial survival effect of platinum-based chemotherapy. Cisplatin and carboplatin have been successfully used with other drugs in a wide variety of well-established two-drug combinations while three-drug combinations are still under investigation. Cisplatin and carboplatin use is limited by toxicity and inherent resistance. These considerations have prompted research into new platinum agents, such as the trinuclear platinum agent BBR3464, the platinum complex ZD0473 and oxaliplatin. These compounds could be developed in combination with agents such as paclitaxel, gemcitabine or vinorelbine in patients with advanced and/or refractory solid tumours.

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Radiosensitization by cytotoxic drugs. The EORTC experience by the Radiotherapy and Lung Cancer Cooperative Groups

Cited by 34 publications

References 11 publications

Chemo‐radiotherapy for advanced non‐small cell lung cancer: concurrent or sequential? It's no longer the question: a systematic review

Chemo‐radiotherapy for advanced non‐small cell lung cancer: concurrent or sequential? It's no longer the question: a systematic review

Accelerated regrowth of non-small-cell lung tumours after induction chemotherapy

Platinum drugs in the treatment of non-small-cell lung cancer

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