Gemcitabine monotherapy in elderly patients with advanced non-small cell lung cancer A multicenter phase II study

Ricci, Sergio; Antonuzzo, Andrea; Galli, Luca; Tibaldi, Carmelo; Bertuccelli, M.; Pegna, Andrea Lopes; Petruzzelli, Stefano; Algeri, R; Bonifazi, V; Fioretto, M.L; Orlandini, Cinzia; Conte, Pierfranco

doi:10.1016/s0169-5002(99)00098-7

Cited by 81 publications

(39 citation statements)

References 18 publications

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“…Indeed, an MST of 5.7 months and a 25% 1-year SR were reported for patients treated with GEM in a randomised study comparing this drug to the best supportive care . In a phase II study restricted to patients aged more than 70 years, an MST of 6.7 months was achieved with GEM alone (Ricci et al, 2000). Moreover, Quoix (Quoix et al, 2003) recently explored in elderly patients the activity of two different schedules of gemcitabine (either 1000 mg m À2 for 3 consecutive weeks every 4 weeks, or 1125 mg m À2 for 2 consecutive weeks every 3 weeks), reporting a MST of 5.1 and 6.8 months, respectively.…”

Section: Discussionmentioning

confidence: 99%

“…Single agent paclitaxel was also demonstrated to produce a 2-month longer MST (6.8 vs 4.8 months) in comparison with supportive care in a randomised trial with no upper limit of age for accrual (Ranson, 2000), and this drug appeared highly attractive for treating elderly patients, in view of the increasing evidence that a weekly schedule may improve its toxicity profile (Alberola et al, 2002). Furthermore, retrospective (Martin et al, 1997;Shepherd et al, 1997) and prospective studies (Altavilla et al, 2000;Anderson et al, 2000;Ricci et al, 2000) have also supported the use of gemcitabine in elderly NSCLC patients, given its good tolerability and activity regardless of age.…”

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confidence: 99%

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Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients

Comella

Frasci

Carnicelli³

et al. 2004

Br J Cancer

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The aim of this study was to assess whether a combination of gemcitabine (GEM) with either paclitaxel (PTX) or vinorelbine (VNR) could be more effective than GEM or PTX alone in elderly or unfit advanced non-small-cell lung cancer (NSCLC) patients. A total of 264 NSCLC patients aged 470 years with ECOG performance status (PS)p2, or younger with PS ¼ 2, were randomly treated with: GEM 1200 mg m À2 on days 1, 8 and 15 every 28 days; PTX 100 mg m À2 on days 1, 8 and 15 every 28 days; GEM 1000 mg m À2 plus PTX 80 mg m À2 (GT) on days 1 and 8 every 21 days; GEM 1000 mg m À2 plus VNR 25 mg m À2 (GV) on days 1 and 8 every 21 days. In all arms, an intra-patients dose escalation was applied over the first three courses, provided that no toxicity of WHO grade X2 had previously occurred. At present time, 217 (82%) patients had died. The median (months) and 1-year survival probability were 5.1 and 29% for GEM, 6.4 and 25% for PTX, 9.2 and 44% for GT, and 9.7 and 32% for GV. Multivariate analysis showed that PSp1 (hazard ratio (HR) ¼ 0.67; 95% CI 0.51 -0.90), and doublet treatments (HR ¼ 0.76; 95% CI 0.59 -0.99) were significantly associated with longer survival. Doublets produced no more toxicity than single agents. GT should be considered a reference regimen for elderly NSCLC patients with PSp1.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients

Comella

Frasci

Carnicelli³

et al. 2004

Br J Cancer

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“…An overall response rate of 20% was observed in the Manchester/Copenhagen study (and verified by an independent oncology review board), and 51 out of 73 patients (70%) reported an improvement in their tumour related symptoms (Anderson et al, 1994). Single agent gemcitabine has been studied in the elderly with advanced NSCLC (Pasquini et al, 1998;Ricci et al, 2000). Response rates and toxicity profiles were no different from other phase II studies of single agents in younger patients.…”

Section: Clinical Effectiveness Of Gemcitabinementioning

confidence: 85%

The case for the introduction of new chemotherapy agents in the treatment of advanced non small cell lung cancer in the wake of the findings of The National Institute of Clinical Excellence (NICE)

Waters

O’Brien

2002

Br J Cancer

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After years of nihilism towards the use of chemotherapy for non small cell lung cancer in the UK it would appear that we have now reached the point where the use of chemotherapy to relieve symptoms, maintain quality of life, and prolong life, are now accepted for informed patients with good performance status willing to accept short-term toxicities. The use of the new agents vinorelbine, gemcitabine and paclitaxel in combination with cisplatin or carboplatin are all active regimens which offer small but real advantages over standard UK triple therapies (MVP, MIC) in terms of resource use, toxicity profiles and response rates. Overall survival could be increased by as much as 10% at one year on indirect comparisons. The use of docetaxel as second line therapy now offers lung cancer patients a second bite of the cherry, and should overall also prolong survival. It is only in embracing these small gains that we can currently make progress in the treatment of NSCLC. The widespread nihilism in the UK towards palliative lung cancer treatment has meant that patients with all stages of lung cancer have been deprived of treatment that adds small survival gains and improved symptom relief. This may contribute to the overall dismal outcome survival figures for lung cancer in the UK (Janssen-Heijnen et al, 1998). At this time chemotherapy is sufficiently active to justify its use in patients of good performance status who understand the true goals of chemotherapy and its potential toxicities -but what should we use? The current questions regarding palliative chemotherapy in the UK remain -is any doublet of the new or old generation better than UK triple therapy for patients of performance status zero or one, and can single agent chemotherapy replace UK triple therapy for patients of performance status two? This review will examine the data in support of the new agents that have been assessed by the National Institute of Clinical Excellence in an attempt to answer these questions. CURRENT STANDARDSThe commonest (standard) treatments for non-small cell lung cancer (NSCLC) in this country are cisplatin based, usually MVP (mitomycin C, vinblastine and cisplatin) or MIC (mitomycin C, iphosphamide and cisplatin) with cisplatin used at a dose of around 50 -60 mg m 72. This differs to the United States where the cisplatin dose is usually higher and the combinations most frequently used until the late 1990s were etoposide plus cisplatin and vinblastine or vindesine with cisplatin. These regimens have been directly compared in several trials. One of these trials compared MIC, MVP and etoposide/cisplatin and showed a significant survival advantage for both three drug regimens (median survival 36 weeks, 42 weeks, and 27 weeks respectively; P50.04) (Crino et al, 1995). Other randomised trials did not report any advantages with the cisplatin triplets (Ruckdeschel et al, 1986;Crino et al, 1990).The use of higher cisplatin doses was based on one small randomised trial involving 85 patients, that demonstrated a longer duration of response a...

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“…Cisplatin plus gemcitabine regimen has become a commonly used combination for advanced NSCLC (22) and maintenance therapy (23). When used as a first-line monotherapy, the objective response rate to gemcitabine is 16-22% (24). Thus, developing novel adjuvant chemotherapy in combination with gemcitabine chemotherapy is urgent.…”

Section: Discussionmentioning

confidence: 99%

Knockdown of Cul4A increases chemosensitivity to gemcitabine through upregulation of TGFBI in lung cancer cells

Hung

Chen

et al. 2015

Oncology Reports

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Abstract. Cullin 4A (Cul4A) promotes oncogenesis through overexpression and then ubiquitination-mediated proteolysis of tumor suppressors in various types of cancers. Transforming growth factor β-induced (TGFBI) has been implicated as a tumor suppressor, which enhances gemcitabine chemosensitivity in lung cancer cells. The present study aimed to investigate the association of TGFBI and Cul4A and the mechanism by which Cul4A regulates TGFBI. In addition, we also evaluated the therapeutic value of Cul4A RNAi using adenoviral transfection of Cul4A RNAi in nude mouse xenograft models. We observed that knockdown of Cul4A was associated with increased sensitivity to gemcitabine through upregulation of TGFBI in lung cancer cells. Cul4A regulated TGFBI through direct interaction and then ubiquitin-mediated protein degradation. In the nude mouse xenograft models, adenoviral transfection of Cul4A RNAi in combination with gemcitabine chemotherapy inhibited lung cancer tumor growth. As the result, combination of Cul4A RNAi with chemotherapy may provide a new approach to lung cancer treatment.

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Gemcitabine monotherapy in elderly patients with advanced non-small cell lung cancer A multicenter phase II study

Cited by 81 publications

References 18 publications

Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients

Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients

The case for the introduction of new chemotherapy agents in the treatment of advanced non small cell lung cancer in the wake of the findings of The National Institute of Clinical Excellence (NICE)

Knockdown of Cul4A increases chemosensitivity to gemcitabine through upregulation of TGFBI in lung cancer cells

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