Weekly gemcitabine and cisplatin in advanced non-small-cell lung cancer: A phase II study

Lippe, P.; Tummarello, Diego; Monterubbianesi, Maria Cristina; Silva, R. R.; Giuliodori, Luciano; Mari, D.; Santo, Antonio; Pasini, Felice; Cetto, Gian Luigi; Rossi, David; Porfiri, Emilio; Cascinu, Stefano; Cellerino, R

doi:10.1023/a:1008323604269

Cited by 23 publications

(11 citation statements)

References 16 publications

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“…Given the good tolerability and the efficacy of a weekly gemcitabine and cisplatin regimen that we employed in patients aged 65 years or less [3], we planned to evaluate the same drug schedule in patients aged 70 years or more.…”

Section: Discussionmentioning

confidence: 99%

“…In our previous trial we observed partial responses in 12 out of the 30 evaluable patients (40%, with 95% CI 22.5–57.5%) [3]. …”

Section: Discussionmentioning

confidence: 99%

“…Here we report the results of a prospective trial in which we treated 48 patients with NSCLC aged 70 years or more, with a regimen based on the weekly administration of cisplatin and gemcitabine [3]. We employed weekly administration of cisplatin after the suggestion from published literature that this might increase cisplatin activity [4, 5, 6, 7]with a more favorable toxicity profile and a simpler administration procedure.…”

Section: Introductionmentioning

confidence: 99%

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Elderly Patients with Advanced Non-Small Cell Lung Cancer

Berardi¹,

Porfiri²,

Scartozzi³

et al. 2003

Oncology

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Objectives: The incidence of non-small cell lung cancer (NSCLC) is increasing among the elderly. We studied the toxicity and efficacy of a weekly schedule of gemcitabine and cisplatin in elderly patients with advanced NSCLC. Methods: Patients aged 70 years or above with advanced NSCLC were treated in a phase II prospective trial with gemcitabine 1,000 mg/m² and cisplatin 35 mg/m² on days 1, 8 and 15 every 28 days. Results: Forty-eight patients with a median age of 74 years (range 70–78) participated in the study. We observed 14 cases with partial response, 14 with stable disease and 16 with progressive disease, whilst 4 patients were not evaluable. By intention-to-treat analysis, partial response rate was 31.8% whilst progressive disease was 33.3%. Median survival was 9 months; 1-year survival probability was 34.4% and median time to progression was 4 months. Grade III–IV leukopenia was observed in 5/48 patients (10.4%), 20/48 patients (41.7%) had grade III–IV thrombocytopenia and 7/48 patients (14.6%) had grade III–IV anemia. One patient experienced grade III emesis and 2 patients had grade III–IV fatigue. Conclusions: At this dose and schedule the combination of gemcitabine and cisplatin appears to be an active and well-tolerated regimen for elderly patients with advanced NSCLC.

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Section: Discussionmentioning

confidence: 99%

“…In our previous trial we observed partial responses in 12 out of the 30 evaluable patients (40%, with 95% CI 22.5–57.5%) [3]. …”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Elderly Patients with Advanced Non-Small Cell Lung Cancer

Berardi¹,

Porfiri²,

Scartozzi³

et al. 2003

Oncology

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“…Furthermore, this schedule may facilitate the synergistic interaction between gemcitabine and cisplatin. A number of trials of 28-day regimens report frequent dose modifications and omissions, particularly on day 15 in bladder and lung cancer (13,20,21). Optimising the delivered dose while minimizing dose delays and dose modifications due to toxicity are likely to have an impact on disease-free and overall survival (18).…”

Section: Discussionmentioning

confidence: 99%

A study of split-dose cisplatin-based neo-adjuvant chemotherapy in muscle-invasive bladder cancer

et al. 2012

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Abstract. The aim of this study was to investigate the outcome of patients with muscle-invasive bladder cancer (MIBC) receiving neo-adjuvant chemotherapy (neo-CT) using a cisplatin-based regimen fractionated on days 1 and 8 of a 21-day cycle prior to organ-preservation (chemoradiation) or cystectomy. Patients with stage T2-T4, N0, M0, transitional cell carcinoma (TCC) of the bladder with a calculated glomerular filtration rate (GFR) ≥40 ml/min were eligible for inclusion in the study. Neo-CT comprised of gemcitabine (1,000 mg/m 2 d1, d8, q21) plus cisplatin (35 mg/m 2 d1, d8, q21) for four cycles. Following the administration of neo-CT, patients underwent surgery or radiotherapy (RT) with or without concurrent chemotherapy (CRT), based on the response to neo-CT and clinician and patient preference. A total of 23 patients were recruited: 21 males and 2 females; median age, 69 years (range, 49-85); stage T2=11, T3A=7, T3B=5, grade 2=1, grade 3=22. One patient progressed prior to neo-CT. In total, 75 cycles of neo-CT were administered. Treatment was well-tolerated with only one episode of neutropenic sepsis. Three of 22 patients developed early progression and did not receive radical treatment. For the remaining 19 patients, choice of definitive treatment (surgery vs. RT/CRT) was based on response to neo-CT. Eight patients had residual disease at cystoscopy following the completion of neo-CT; six patients underwent surgery and two underwent RT/CRT. A total of 11 patients had a complete response (CR) to neo-CT, nine of whom were treated by RT/CRT, with the remaining two declining radical treatment. Median follow-up for alive patients was 57 months (range, 4.4-68.5). Three-year survival was 37% (95% CI 17-58%) and 5-year survival was 31% (95% CI 15-52%). Neo-CT is effective and well-tolerated in MIBC. This split-dose cisplatin regimen facilitates treatment in an outpatient setting and allows inclusion of patients with compromised GFR. IntroductionBladder cancer is the second most common genitourinary malignancy and is a significant cause of morbidity and mortality. Almost 25% of patients have muscle-invasive disease at presentation (1,2). In North America, the treatment of choice for muscle invasive bladder cancer is radical cystectomy and bilateral pelvic lymph node dissection. Although surgery may be curative, approximately 50% of all patients with muscle invasive transitional cell carcinoma (TCC) develop metastatic disease within 2 years of cystectomy and subsequently succumb to the disease, presumably due to a significant proportion of patients harboring micrometastatic disease (3). On this basis, neo-adjuvant and adjuvant chemotherapy have been tested in numerous phase II and a few phase III studies (4-7).There are two principal rationales for neo-adjuvant chemotherapy: i) to improve survival in patients with micrometastatic disease and ii) to preserve the bladder by shrinking the primary tumour to facilitate radiotherapy as an alternative definitive therapy to surgery (8). The results of the South Western Oncol...

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“…In all these tumour types, including NSCLC, further improvement of therapy with cisplatin has been extensively investigated. Cisplatin has been used in combinations with other different chemotherapeutic agents, such as DNA-alkylators, topoisomerase II inhibitors, vinorelbine and gemcitabine (Fukuoka et al, 1992;Liu, 1993;Sculier et al, 1994;Gridelli et al, 1996;Wozniak et al, 1998;Lippe et al, 1999). Besides evaluation of different combinations of cisplatin, important other approaches have focused on increasing the dose and/or the dose intensity of the drug using higher doses per course (Klastersky et al, 1986;Gandara et al, 1993), or shortening the treatment interval (Planting et al, 1993(Planting et al, , 1994(Planting et al, , 1995a(Planting et al, , b, 1996a(Planting et al, , b, 1997(Planting et al, , 1999.…”

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Adaptive intrapatient dose escalation of cisplatin in combination with low-dose vp16 in patients with nonsmall cell lung cancer

et al. 2003

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The objective of this phase II and pharmacologic study was to explore the feasibility, toxicity and activity of adaptive intrapatient dose escalation of cisplatin in a dose-intensive weekly schedule using predefined levels of exposure, with the ultimate aim to improve the antitumour activity of the therapy in patients with nonsmall cell lung cancer (NSCLC). Platinum DNA-adduct levels in peripheral white blood cells during treatment were used as the primary parameter for adaptive dosing. If DNA-adduct levels were not available, the area under the concentration -time curve (AUC) of unbound platinum in plasma was used for dose adaptation. Target levels for DNA-adducts and AUC have been defined in a previously performed pharmacologic study. The feasibility of adaptive dosing was tested in 76 patients with stage IIIB and IV NSCLC, who were planned to receive 6 weekly courses of cisplatin at a starting dose of 70 mg m À2 , together with daily low oral dose of 50 mg VP16. In total, 37 patients (49%) who were given more than one course received a dose increase varying from 10 to 55%. The majority of patients reached the defined target levels by a dose increase during course two. Relevant grade 2 neurotoxicity was observed in eight (10%) patients and reversible ototoxicity grade 2 in 14 (18%) patients. The strategy of adaptive intrapatient dose adjustment of cisplatin is practically feasible in a research setting even when results for dose adaptation have to be reported within a short time-period of 1 week. The toxicity appeared to be manageable in this cohort of patients. In some patients, exposure after the standard dose was substantially lower than the defined target level and significant dose escalations of more than 50% had to be applied. The response rate (RR) was relatively high: overall 40% (29 out of 72 patients) partial remission (PR), in patients with stage IIIB the RR was 60% (15 out of 25 patients) and with stage IV 30% (14 out of 47 patients). Randomised studies are needed to determine whether the adaptive dosing strategy results in better efficacy than standard dosing.

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Weekly gemcitabine and cisplatin in advanced non-small-cell lung cancer: A phase II study

Abstract: This regimen appears to be active and to have a favourable toxicity profile.

Cited by 23 publications

References 16 publications

Elderly Patients with Advanced Non-Small Cell Lung Cancer

Elderly Patients with Advanced Non-Small Cell Lung Cancer

A study of split-dose cisplatin-based neo-adjuvant chemotherapy in muscle-invasive bladder cancer

Adaptive intrapatient dose escalation of cisplatin in combination with low-dose vp16 in patients with nonsmall cell lung cancer

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