Twice-Daily Compared with Once-Daily Thoracic Radiotherapy in Limited Small-Cell Lung Cancer Treated Concurrently with Cisplatin and Etoposide

Turrisi, Andrew T.; Kim, KyungMann; Blum, Ronald H.; Sause, William T.; Livingston, Robert B.; Komaki, Ritsuko; Wagner, Henry; Aisner, Seena C.; Johnson, David H.

doi:10.1056/nejm199901283400403

Cited by 1,335 publications

(883 citation statements)

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“…This may have been due to the higher total RT doses used in the head and neck (60 -70 Gy), although we could not establish clearly a dose-response relation, the higher response to induction therapy, or both. Although there is evidence that concurrent chemoradiation rather than sequential chemoradiation is a more effective method for inducing a complete clinical response in patients with small cell lung carcinoma, [25][26][27] sequential chemoradiation appears to be an adequate and less toxic means of securing local control for most patients with NSNEC.…”

Section: Discussionmentioning

confidence: 99%

Management of nonsinonasal neuroendocrine carcinomas of the head and neck

Barker¹,

Glisson²,

Garden³

et al. 2003

Cancer

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BACKGROUNDNonsinonasal neuroendocrine carcinomas (NSNEC) of the head and neck are rare and pose a diagnostic and management challenge. The authors undertook a retrospective study to gain insights into the spectrum of clinicopathologic characteristics, patterns of failure, and optimal management of patients with this disease.METHODSThe authors treated 23 adults with pathologically proven, nonmetastatic, primary NSNEC from 1984 to 2001. The majority (13 patients) had laryngeal origin with the following American Joint Committee on Cancer stage distribution: Stage I disease in 1 patient, Stage II disease in 2 patients, Stage III disease in 6 patients, and Stage IV disease in 14 patients. Nine patients underwent definitive surgery with or without postoperative radiation, and 14 patients received definitive radiotherapy. The median definitive radiation dose was 66 grays (Gy) (range, 44–72 Gy) using conventional fractionation. Fourteen patients received chemotherapy, with two to four cycles of induction platinum plus etoposide used most commonly.RESULTSThe median follow‐up time for surviving patients was 40 months (range, 15–89 months). The actuarial 2‐year and 5‐year overall survival (OS) rates were 53% and 33%, respectively; and the disease‐free survival (DFS) rates were 41% and 25%, respectively. Both the 2‐year OS rate (68% vs. 30%; P = 0.002) and the 2‐year DFS rate (55% vs. 17%; P = 0.004) were improved with chemotherapy compared with local therapy alone. Seventy‐five percent of patients with measurable disease had complete clinical responses to induction chemotherapy. There was 100% complete clinical response of tumor after radiotherapy. The actuarial 2‐year local failure rate was 23%. Chemotherapy did not reduce local failure (P = 0.91). There was no regional failure. The 2‐year and 5‐year distant metastasis rates were 54% and 71%, respectively. The 2‐year rates of metastases without and with chemotherapy were 79% and 39%, respectively (P = 0.006). The 2‐year and 5‐year rates of intracranial metastases were 25% and 44%, respectively, and the 2‐year and 5‐year rates of isolated brain metastases were 21% and 41%, respectively.CONCLUSIONSBased on these results, the authors' treatment strategy for patients with NSNEC is sequential chemotherapy and radiation. They recommend full‐dose radiotherapy alone for patients with NSNEC who achieve a complete clinical response to induction chemotherapy. Newer chemotherapeutic regimens or additional adjuvant chemotherapy should be investigated for patients with NSNEC given the high rate of distant failure. Due to the very high rate of brain metastases among patients in the current study, the authors now consider incorporating prophylactic cranial irradiation into primary radiotherapy for individual patients who have complete clinical responses to induction chemotherapy. Cancer 2003. © 2003 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Management of nonsinonasal neuroendocrine carcinomas of the head and neck

Barker¹,

Glisson²,

Garden³

et al. 2003

Cancer

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“…Aggressive radiotherapy or concurrent chemo-radiation therapy for lung cancer is standard care for patients with locally advanced disease, i.e. stage III non-small cell lung cancer (NSCLC) or limited stage small cell lung carcinoma (LD-SCLC) [3,4].Combined concurrent modality treatment increases long-term survival, but at the expense of a higher incidence of severe esophagitis [5][6][7][8]. In order to allow proper balancing between expected benefits and drawbacks of aggressive therapy, knowledge of the effects of a given treatment on the quality of life (QoL) is needed.…”

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confidence: 99%

High-dose radiotherapy or concurrent chemo-radiation in lung cancer patients only induces a temporary, reversible decline in QoL

Pijls‐Johannesma

Houben

Boersma

et al. 2009

Radiotherapy and Oncology

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a b s t r a c tBackground and purpose: Aggressive radiotherapy or concurrent chemo-radiation therapy for lung cancer leads to a high incidence of severe, mostly esophageal, toxicity. The purpose of this study was to investigate the evolution of quality of life (QoL) in patients with lung cancer, selected for curative radiotherapy (RT) or chemo-RT. Methods: Seventy-five lung cancer patients completed a longitudinal the EORTC QLQ-C30 and LC13. Linear mixed regression models were fitted to investigate the impact of different factors on overall QoL. Results: Overall QoL decreased shortly after the end of RT (4 points, p = 0.19), but increased back to baseline within 3 months. Mean scores of role functioning (p = 0.018), cognitive functioning (p = 0.002), dyspnoea (EORTC QLQ-LC13; p = 0.043), dysphagia (p = 0.005) and hoarseness (p = 0.029), showed a significant worsening over time. Emotional functioning (p = 0.033) improved significantly over time. Severe esophagitis (Pgrade 2) was reported in only 12% of the patients. Next to maximal esophageal toxicity Pgrade 2 (p = .0.010), also tumor stage IIIA (p < 0.001), tumor stage IIIB (p = 0.003), gender (p = 0.042) and fatigue (p < 0.001) appeared to be significant predictors of QoL. Conclusion: High-dose radiotherapy or concurrent chemo-radiation in the treatment of lung cancer seems to be a well-tolerated treatment option with preservation of QoL. Lung cancer remains a major public health problem worldwide because of its high incidence, rapid progression, and poor outcome [1]. The majority of patients who develop lung cancer die of this disease within a year [2]. Aggressive radiotherapy or concurrent chemo-radiation therapy for lung cancer is standard care for patients with locally advanced disease, i.e. stage III non-small cell lung cancer (NSCLC) or limited stage small cell lung carcinoma (LD-SCLC) [3,4].Combined concurrent modality treatment increases long-term survival, but at the expense of a higher incidence of severe esophagitis [5][6][7][8]. In order to allow proper balancing between expected benefits and drawbacks of aggressive therapy, knowledge of the effects of a given treatment on the quality of life (QoL) is needed.An optimal therapy could be defined as one that increases survival or provides benefit through reduction in cancer-related symptoms and improved QoL.To the best of our knowledge, in only one study, QoL assessment was performed in patients receiving high-dose radiotherapy for NSCLC [9]. No data are at present known on the influence of concurrent chemo-radiation on the QoL.Moreover, a broad Medline search using the terms ''QoL and SCLC" (December 2008) revealed only 15 studies of which none examined QoL after radiotherapy treatment.The purpose of this study was to investigate the evolution of QoL on NSCLC stages I-III and LD-SCLC patients, referred for hyperfractionated accelerated high-dose radiotherapy (RT) with or without concurrent chemotherapy, with curative intent. Since we hypothesized that QoL would be considerably influenced by esophageal...

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“…1,[15][16][17][18][19] To administer this three-drug combination safely, doses of all three drugs were reduced compared with the doses feasible in various two-drug combinations. Even with the routine use of granulocyte-colony stimulating factor (G-CSF), our previous Phase I trial demonstrated that dose-limiting thrombocytopenia prevented meaningful dose escalation.…”

Section: Discussionmentioning

confidence: 99%

“…Improved methods of combining chemotherapy and radiation therapy have resulted in survival improvements for patients with limited stage small cell lung carcinoma: recent large trials have documented a median survival of 20 -24 months, with 20% of patients disease free at 4 -5 years. 1 During the last several years, the introduction of several active new agents has led to improvements in therapy for patients with a number of epithelial malignancies. Several of these new drugs, including the taxanes, topotecan, irinotecan, and gemcitabine, are active in the first-line treatment of patients with extensive stage small cell lung carcinoma, with response rates ranging from 20% to 50%.…”

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confidence: 99%

Paclitaxel, carboplatin, and topotecan in the treatment of patients with small cell lung carcinoma

Hainsworth

Morrissey

Scullin³

et al. 2002

Cancer

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BACKGROUNDThe objective of this study was to evaluate the feasibility, toxicity, and efficacy of a novel three‐drug regimen containing paclitaxel, carboplatin, and topotecan followed by oral etoposide in the first‐line treatment of patients with small cell lung carcinoma.METHODSOne hundred five patients with previously untreated, limited stage or extensive stage small cell lung carcinoma were treated in this multicenter, community‐based, Phase II trial. All patients received paclitaxel 135 mg/m2 by 1‐hour intravenous (IV) infusion on Day 1, carboplatin at an area under the serum concentration‐time curve of 5.0 IV on Day 1, and topotecan 0.75 mg/ m2 IV on Days 1–3. The treatment regimen was repeated at 21‐day intervals for 4 courses. Patients with limited stage disease also received radiation therapy (45 grays [Gy]; in single daily fractions of 1.8 Gy) beginning concurrently with the third course of chemotherapy. Patients who had an objective response or stable disease after 4 courses of combined paclitaxel, carboplatin, and topotecan then received 3 courses of oral etoposide (50 mg alternating with 100 mg for 10 consecutive days) repeated at 21‐day intervals.RESULTSTreatment with paclitaxel, carboplatin, and topotecan produced response rates of 88% and 93% in patients with extensive stage disease and limited stage disease, respectively. The median survival for patients with extensive stage and limited stage disease was 8.3 months and 17.2 months, respectively. The addition of oral etoposide was feasible, but there was no suggestion that it prolonged remission. This three‐ drug regimen was associated with acceptable toxicity in patients with a good performance status, although it was tolerated very poorly by patients with an Eastern Cooperative Oncology Group performance status of 2; 5 of 12 patients (42%) had treatment‐related deaths.CONCLUSIONSAlthough this three‐drug regimen was active in the treatment of patients with small cell lung carcinoma, it was more toxic than standard platinum and etoposide regimens and provided no apparent improvement in efficacy. Further investigation of topotecan as a component of first‐line therapy should focus on two‐drug combination regimens in which the topotecan dose can be optimized. Routine use of three‐drug regimens in patients with small cell lung carcinoma should await demonstration of superiority in randomized trials. Cancer 2002;94:2426–33. © 2002 American Cancer Society.DOI 10.1002/cncr.10508

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Twice-Daily Compared with Once-Daily Thoracic Radiotherapy in Limited Small-Cell Lung Cancer Treated Concurrently with Cisplatin and Etoposide

Cited by 1,335 publications

References 23 publications

Management of nonsinonasal neuroendocrine carcinomas of the head and neck

Management of nonsinonasal neuroendocrine carcinomas of the head and neck

High-dose radiotherapy or concurrent chemo-radiation in lung cancer patients only induces a temporary, reversible decline in QoL

Paclitaxel, carboplatin, and topotecan in the treatment of patients with small cell lung carcinoma

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