A randomised phase II study of the efficacy and safety of intravenous topotecan in combination with either cisplatin or etoposide in patients with untreated extensive disease small-cell lung cancer

Quoix, Élisabeth; Breton, Jean-Luc; Gervais, Radj; Wilson, Jonathan; Schramel, Franz M.N.H.; Cardenal, Felipe; Ross, Graham; Preston, A.; Lymboura, Margarita; Mattson, K.

doi:10.1016/j.lungcan.2005.02.008

Cited by 28 publications

(12 citation statements)

References 23 publications

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“…Topotecan, another member of the camptothecin family, has been evaluated in several phase II and III trials as first-line therapy for ES-SCLC in comparison with the standard treatment of EP [23,24,37]. These trials concluded noninferiority of cisplatin/topotecan compared to EP with regard to overall survival.…”

Section: Alternatives To Platin/etoposidementioning

confidence: 99%

Treatment of extensive-stage small cell lung carcinoma: current status and future prospects

Demedts

Vermaelen²,

Meerbeeck³

2009

European Respiratory Journal

183

162

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Small cell lung cancer (SCLC) is an aggressive lung tumour strongly associated with cigarette smoking, with patients often presenting with metastatic disease at the time of diagnosis. Although SCLC is very chemoradiosensitive and high response rates are obtained with treatment, relapse rates are high and the prognosis remains very poor.In limited-stage SCLC, the overall survival rate has been significantly improved by adding dosehyperfractionated thoracic radiotherapy and prophylactic cranial irradiation to systemic chemotherapy. In contrast, little progress has been made in the treatment of extensive-stage SCLC (ES-SCLC), apart from the recently documented survival gain by the addition of prophylactic cranial irradiation.First-line therapy in ES-SCLC currently consists of chemotherapy, combining a platinum drug with either etoposide or irinotecan as a possible alternative.New treatments are needed in order to improve the prognosis of ES-SCLC, as median survival with current standard treatment is still only 9-10 months from diagnosis. The present review focuses on the management of ES-SCLC, with special attention to the development of new treatment options.KEYWORDS: Chemotherapy, extensive disease, radiotherapy, small cell lung cancer, treatment S mall cell lung cancer (SCLC) is an aggressive malignant disease, with the majority of patients presenting with distant metastasis at diagnosis. A separate staging system has been developed for SCLC, classifying SCLC as limited or extensive disease [1]. The International Association for the Study of Lung Cancer defines limited-stage SCLC (LS-SCLC) as: ''disease restricted to one hemithorax with regional lymph node metastases, including hilar, ipsilateral and contralateral mediastinal, and ipsilateral and contralateral supraclavicular nodes and should also include patients with ipsilateral pleural effusion independent of whether cytology is positive or negative '' [2]. Patients with SCLC who do not fit this definition are considered to have extensive-stage SCLC (ES-SCLC). This staging system was used to select the appropriate treatment regimen: chemotherapy in combination with thoracic radiotherapy in patients with LS-SCLC, and chemotherapy alone in patients with ES-SCLC. Recent data suggest that the tumour, node, metastasis classification traditionally reserved for the staging of nonsmall cell lung cancer (NSCLC) can also be applied for the staging of SCLC [3].

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Section: Alternatives To Platin/etoposidementioning

confidence: 99%

Treatment of extensive-stage small cell lung carcinoma: current status and future prospects

Demedts

Vermaelen²,

Meerbeeck³

2009

European Respiratory Journal

183

162

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“…In untreated ED-SCLC patients comparable results in response with manageable toxicity were achieved with the combination of topotecan + cisplatin or etoposide in a randomized phase II trial [7]. On the basis of these results this phase III study aimed to evaluate the efficacy, feasibility and safety of topotecan/cisplatin (TP) compared to the standard fi rst-line chemotherapy, etoposide/ cisplatin.…”

Section: Topotecan (T) In Es-sclc -Phiii: Fi Nal Results Of Tp Vs Epmentioning

confidence: 99%

Small cell lung cancer

Ploner

2008

memo

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memo Small cell lung cancer 4/2008 ASCO Update -SCLC 243 SCLC is a life-threatening disease, typically caused by cigarette smoking. Th e incidence has been decreasing during the past decades, probably due to changes in smoking habits. Th e disease is mostly diagnosed in advanced stage and therefore requires systemic treatment and radiotherapy. Chemotherapy is the most important treatment intervention and a combination of cisplatin + etoposide (EP) represents the standard of care. Th ese tumours are very sensitive to primary treatment with remarkable response rates, although usually of short duration due to resistance. Improvement in outcomes is very hard to obtain in this disease, regardless of treatment intervention -as it has been recognised in the past years.Th e presentations at this year's ASCO on SCLC underline this dilemma: results of 3 large phase III trials investigating alternative combination chemotherapy regimens with irinotecan, pemetrexed and topotecan failed to improve outcome when compared to standard treatment with EP. A further report of a phase III trial underlined the current standard of 25 Gy PCI dose in LD-SCLC complete responders with no additional benefi t of a higher PCI dose.Progress in the treatment of SCLC -if any -remains to be slow in the light of the presented results.

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“…Topotecan in combination with standard chemotherapy A summary of further studies of topotecan in combination or as consolidation chemotherapy in sequential or alternating schedules is outlined in Table 1. A randomised phase II trial compared a non-platinum combination of topotecan/etoposide to topotecan/cisplatin in 82 previously untreated SCLC patients [19]. Disappointingly, response rates and median survival times were not statistically different, and there was significant myelosuppression in both groups (grade 3/4 neutropenia rates of 65 and 56%, respectively).…”

Section: Clinical Use Of Topotecanmentioning

confidence: 99%

Therapeutic uses of topotecan for thoracic malignancies

et al. 2009

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Topotecan, a topoisomerase 1 inhibitor (topo1-i), is a semi-synthetic derivative of camptothecan with wellestablished cytotoxic properties. It is licensed for the treatment of relapsed, sensitive small cell lung cancer (SCLC) and for second line treatment in ovarian cancer. Studies have also shown this drug to be an effective first line treatment for SCLC with either cisplatin or in combination with a topoisomerase 2 inhibitor (topo2-i), etoposide; both combinations have shown similar efficacy. Oral and parenteral formulations of topotecan have proven to be equivocal in relapsed SCLC patients. The parenteral form showed reduced rates of severe haematological toxicities and better symptom control than an anthracycline combination (CAV). In relapsed SCLC, a randomised phase III trial of oral topotecan versus best supportive care showed a statistically significant increase in overall survival. In the second line treatment of non-small cell lung cancer (NSCLC), oral topotecan was not inferior to the current standard iv docetaxel for 1 year survival rates. Worthwhile potential investigations include combining oral topotecan with other oral agents to design treatments for different lines of therapy. The new oral formulation of topotecan also lends itself to testing with small molecule tyrosine kinase inhibitors. The myelosuppressive toxicity profile needs to be vigorously monitored and managed. The trials with oral topotecan have also highlighted the need to reassess the utility of the terms 'sensitive' and 'resistant' in the selection of patients with relapsed small cell lung cancer.

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A randomised phase II study of the efficacy and safety of intravenous topotecan in combination with either cisplatin or etoposide in patients with untreated extensive disease small-cell lung cancer

Cited by 28 publications

References 23 publications

Treatment of extensive-stage small cell lung carcinoma: current status and future prospects

Treatment of extensive-stage small cell lung carcinoma: current status and future prospects

Small cell lung cancer

Therapeutic uses of topotecan for thoracic malignancies

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