Cisplatin-gemcitabine combination in advanced non-small-cell lung cancer: a phase II study.

Crinò, Lucio; Scagliotti, G.; Marangolo, M.; Figoli, F.; Clerici, M.; Marinis, Filippo de; Salvati, Franco; Cruciani, Giorgio; Dogliotti, Luigi; Pucci, Fabio; Paccagnella, Adriano; Adamo, Vincenzo; Altavilla, Giuseppe; Incoronato, Pasquale; Trippetti, M; Mosconi, Anna Maria; Santucci, A; Sorbolini, Sara; Oliva, Cristina; Tonato, Maurizio

doi:10.1200/jco.1997.15.1.297

Cited by 273 publications

(121 citation statements)

References 12 publications

Supporting

Mentioning

114

Contrasting

Unclassified

Order By: Relevance

“…Alternative schedules have been described for a variety of tumours. Some investigators have given cisplatin on days 2 or 15 of a 28 day cycle (Abratt et al, 1997;Crino et al, 1997), or split the cisplatin dose for days 1, 8 and 15 (Shepherd et al, 1997(Shepherd et al, , 2000. Others have shortened the cycle to 21 days, administering cisplatin on day 1 (Rosell et al, 1998) or days 1 and 8 (Nagourney et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma

et al. 2002

View full text Add to dashboard Cite

Our previous phase II study of cisplatin and gemcitabine in malignant mesothelioma showed a 47.6% (95% CI 26.2 -69.0%) response rate with symptom improvement in responding patients. Here we confirm these findings in a multicentre setting, and assess the effect of this treatment on quality of life and pulmonary function. Fifty-three patients with pleural malignant mesothelioma received cisplatin 100 mg m 72 i.v. day 1 and gemcitabine 1000 mg m 72 i.v. days 1, 8, and 15 of a 28 day cycle for a maximum of six cycles. Quality of life and pulmonary function were assessed at each cycle. The best response achieved in 52 assessable patients was: partial response, 17 (33%, 95% CI 20 -46%); stable disease, 31 (60%); and progressive disease, four (8%). The median time to disease progression was 6.4 months, median survival from start of treatment 11.2 months, and median survival from diagnosis 17.3 months. Vital capacity and global quality of life remained stable in all patients and improved significantly in responding patients. Major toxicities were haematological, limiting the mean relative dose intensity of gemcitabine to 75%. This schedule of cisplatin and gemcitabine is active in malignant mesothelioma in a multicentre setting. Investigation of alternative scheduling is needed to decrease haematological toxicity and increase the relative dose intensity of gemcitabine whilst maintaining response rate and quality of life.

show abstract

Section: Discussionmentioning

confidence: 99%

A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma

et al. 2002

View full text Add to dashboard Cite

show abstract

Section: Abstract: Apoptosis; Vesicular Stomatitis Virus; Gemcitabinmentioning

confidence: 99%

“…10 -12 When combined with cisplatin and/or paclitaxel or vinorelbine, gemcitabine therapy shows an objective response rates in 28 -54% and the median survival durations ranged from 38 to 61.5 weeks. [13][14][15][16][17][18] However, the treatment of advanced lung cancer still remains a challenge to medical oncologists.Because of differences in mechanisms of action and toxicity profiles, the combination of the above 2 agents may have clinical potential. The present study was designed to determine whether gemcitabine potentiates the antitumor activity of VSV in vitro using both A549 (human lung adenocarcinoma) and LLC (murine Lewis lung carcinoma) cell lines and in vivo using A549 lung cancer xenografts and the murine syngeneic Lewis lung cancer, and if so, to examine the possible mechanism in the phenomenon, as well as to provide some potential implications for the treatment of human lung cancer.…”

mentioning

confidence: 99%

Induction of apoptosis and tumor regression by vesicular stomatitis virus in the presence of gemcitabine in lung cancer

Wei

Wang

et al. 2004

Intl Journal of Cancer

View full text Add to dashboard Cite

Key words: apoptosis; vesicular stomatitis virus; gemcitabine; lung cancer; chemotherapyLung cancer accounts for about 1.5 million cases worldwide and is the leading cause of cancer-related death in both males and females. Non small cell lung cancer (NSCLC) comprises approximately 75-80% of all lung cancers. Despite aggressive approaches made in the therapy of lung cancer in the past decades, the prognosis of NSCLC remains poor, with 5-year survival rates of 5-14%, even if treated with surgery, radiotherapy and/or chemotherapy. 1-3 Efforts are therefore continuing to develop new and less toxic therapeutic approaches for the treatment of lung cancer.Vesicular stomatitis virus (VSV) is an enveloped, negativesense RNA virus and prototypic member of the family rhabdoviridae. 4 -6 It has been shown to replicate rapidly in vitro and kill selectively a variety of tumor cell lines. An essential, dose-limiting site of chemotherapy is the bone marrow while VSV can selectively kill leukemia cells when cocultured with normal bone marrow cells. 4 Furthermore, VSV exhibits the antitumor activity in both human tumor xenografts in nude mice and syngeneic tumors in the immunocompetent mice. 4,5 Gemcitabine (2Ј,2Ј-diflurodeoxycytidine) is a new deoxycytidine analogue that inhibits DNA synthesis. After cellular uptake, gemcitabine is phosphorylated to its active metabolites, which competitively inhibits DNA chain elongation, leading to DNA fragmentation and cell death. Gemcitabine has shown cytotoxic activity against a wide range of cancer cell lines in vitro and a number of murine and human tumors in vivo. [7][8][9] Gemcitabine monotherapy produced objective response in 20 -25% of patients with advanced NSCLC and has similar efficacy to cisplatin plus etoposide. 10 -12 When combined with cisplatin and/or paclitaxel or vinorelbine, gemcitabine therapy shows an objective response rates in 28 -54% and the median survival durations ranged from 38 to 61.5 weeks. [13][14][15][16][17][18] However, the treatment of advanced lung cancer still remains a challenge to medical oncologists.Because of differences in mechanisms of action and toxicity profiles, the combination of the above 2 agents may have clinical potential. The present study was designed to determine whether gemcitabine potentiates the antitumor activity of VSV in vitro using both A549 (human lung adenocarcinoma) and LLC (murine Lewis lung carcinoma) cell lines and in vivo using A549 lung cancer xenografts and the murine syngeneic Lewis lung cancer, and if so, to examine the possible mechanism in the phenomenon, as well as to provide some potential implications for the treatment of human lung cancer. MATERIAL AND METHODS Cells lines and agentsLLC cells and A549 cells were purchased from American Type Culture Collection (Rockville, MD). They were maintained in monolayer cultures in DMEM and RPMI-1640, respectively, supplemented with 10% heat-inactivated fetal bovine serum (FBS), at 37°C in a humidified atmosphere containing 5% CO 2 . Human umbilical vein endothelial cells (HU...

show abstract

“…In phase II studies, 26 -54% stage IIIB/IV NSCLC patients responded to GC treatment. Good median and 1-year survival have been consistently observed (Abratt et al, 1997;Crino et al, 1997;Einhorn, 1997;Shepherd et al, 1997). Three randomized phase III studies demonstrated the superiority of GC over other chemotherapy regimens (Cardenal et al, 1999;Crino et al, 1999;Sandler et al, 2000).…”

mentioning

confidence: 98%

Gemcitabine and cisplatin in a multimodality treatment for locally advanced non-small cell lung cancer

et al. 2002

View full text Add to dashboard Cite

The role of new cytotoxic agents like gemcitabine has not yet been proven in the neoadjuvant settings. We designed a phase II study to test the feasibility of using gemcitabine and cisplatin before local treatment for stage III non-small cell lung cancer patients. Patients received three cycles of induction chemotherapy of gemcitabine (1000 mg m 72 , days 1, 8, 15) and cisplatin (90 mg m 72 , day 15) every 4 weeks before evaluation for operability. Operable patients underwent radical resection. Inoperable patients and patients who had incomplete resection received concurrent chemoradiotherapy with daily low dose cisplatin. All patients who did not progress after local treatment received three more cycles of adjuvant chemotherapy of gemcitabine and cisplatin. Fifty-two patients received induction treatment. Two patients had complete response and 31 patients had partial response (response rate 63.5%) after induction chemotherapy. Thirty-six patients (69%) were operable. Eighteen patients (35%) had their tumours completely resected. Two patients had pathological complete response. Median overall survival was 19.1 months, projected 1-year survival was 66% and 2-year survival was 34%. Three cycles of gemcitabine and cisplatin is effective and can be used as induction treatment before surgery for locally advanced non-small cell lung cancer patients.

show abstract

Cisplatin-gemcitabine combination in advanced non-small-cell lung cancer: a phase II study.

Abstract: The combination of gemcitabine and cisplatin induced a high response rate in both stage IIIB and IV NSCLC, with modest side effects. The regimen deserves further careful evaluation in a phase III prospective randomized trial.

Cited by 273 publications

References 12 publications

A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma

A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma

Induction of apoptosis and tumor regression by vesicular stomatitis virus in the presence of gemcitabine in lung cancer

Gemcitabine and cisplatin in a multimodality treatment for locally advanced non-small cell lung cancer

Contact Info

Product

Resources

About