Indian Journal of Cancer
Home  ICS  Feedback Subscribe Top cited articles Login 
Users Online :3239
Small font sizeDefault font sizeIncrease font size
Navigate here
  Search
 
  
Resource links
 »  Similar in PUBMED
 »  Search Pubmed for
 »  Search in Google Scholar for
 »Related articles
 »  Article in PDF (363 KB)
 »  Citation Manager
 »  Access Statistics
 »  Reader Comments
 »  Email Alert *
 »  Add to My List *
* Registration required (free)  

 
  In this article
 »  Abstract
 » Introduction
 »  Materials and Me...
 » Results
 » Discussion
 »  References
 »  Article Figures
 »  Article Tables

 Article Access Statistics
    Viewed2550    
    Printed112    
    Emailed0    
    PDF Downloaded430    
    Comments [Add]    
    Cited by others 6    

Recommend this journal

 

  Table of Contents  
SYMPOSIUM: LUNG CANCER
Year : 2012  |  Volume : 49  |  Issue : 2  |  Page : 202-208
 

Gemcitabine in brief versus prolonged low-dose infusion, both combined with carboplatin for advanced non-small cell lung cancer


Department of Medical Oncology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India

Date of Web Publication25-Oct-2012

Correspondence Address:
S K Beniwal
Department of Medical Oncology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.102861

Rights and Permissions

 » Abstract 

Purpose: Gemcitabine in low-dose prolonged infusion is a treatment with documented activity against a variety of tumors. The present study was conducted to evaluate the efficacy and safety of the combination of gemcitabine at a low-dose prolonged infusion in comparison with standard dose gemcitabine with carboplatin in chemonaive patients with advanced non-small cell lung cancer (NSCLC). Materials and Methods: Sixty chemonaive patients with stage IIIB or IV NSCLC were included. Patients were randomly assigned 1:1 to receive 350mg/m 2 gemcitabine in a 6-h infusion on days 1 and 8 and carboplatin area under the serum concentration time curve (AUC) 5 on day 1 versus gemcitabine 1000mg/m 2 on days 1 and 8 and carboplatin AUC 5 on day 1 (3-week cycle both). A total of 118 chemotherapy cycles, with a median of 4 cycles per patient (range 2-6), and 134 chemotherapy cycles, with a median of 4.47 cycles per patient (range 3-6) were administered in standard and low infusional dose arm, respectively. Results: Among patients in the standard arm, 40% had overall response rate (ORR), 33.3% had stable disease and 26.6% had progressive disease, while in low-dose infusional arm, 36.6% had ORR, 36.3% had stable disease and 26.6% had progressive disease (P = 0.992). Median progression-free survival was 5.5 months and 5.4 months, median overall survival was 9.7 months and 10.7 months, and 1-year survival was 33.7% and 36.6% in standard arm and low-dose infusion arm, respectively. Grade 3/4 toxicity was rare. Conclusion: In NSCLC, gemcitabine low-dose prolonged infusion with carboplatin has low toxicity, especially thrombocytopenia, and has an activity comparable with gemcitabine given in higher dose in standard infusion.


Keywords: Deoxycytidine kinase, gemcitabine, prolonged low-dose infusion, standard dose


How to cite this article:
Beniwal S K, Patel K M, Shukla S, Parikh B J, Shah S, Patel A. Gemcitabine in brief versus prolonged low-dose infusion, both combined with carboplatin for advanced non-small cell lung cancer. Indian J Cancer 2012;49:202-8

How to cite this URL:
Beniwal S K, Patel K M, Shukla S, Parikh B J, Shah S, Patel A. Gemcitabine in brief versus prolonged low-dose infusion, both combined with carboplatin for advanced non-small cell lung cancer. Indian J Cancer [serial online] 2012 [cited 2019 Nov 13];49:202-8. Available from: http://www.indianjcancer.com/text.asp?2012/49/2/202/102861



 » Introduction Top


Lung cancer is one of the most common cancers in the world, with over 1 million new cases occurring annually. Furthermore, the Indian Council of Medical Research reports that lung cancer is one of the commonest cancers among Indian men. Most patients present at an advanced stage where 40.6% and the disease is incurable and the intent of treatment is palliative. Platinum-based chemotherapy is considered as the standard treatment for advanced disease. The third-generation agents, such as taxanes and vinorelbine, administered with a platinum derivative, have resulted in improved median and 1-year survival times when compared with either cisplatin alone or older platinum-based combinations in randomized trials. [1],[2],[3]

Gemcitabine is a pyrimidine antimetabolite. It has consistently demonstrated a favourable toxicity profile and activity in advanced non-small cell lung cancer (NSCLC) and it enhances the cytotoxicity of cisplatinum by increasing the formation of cytotoxic platinum-DNA adducts. Gemcitabine-cisplatin chemotherapy is considered as one of the most active regimens for advanced NSCLC, with an overall response rate (ORR) of 22-a median survival of 8.1-9.8 months in phase III trials. [4],[5],[6] Although several phase III trials of new platinum-based doublets [5],[6],[7],[8] have produced similar results, a recent meta-analysis showed an absolute 1-year survival benefit of 3.9% for gemcitabine-cisplatin chemotherapy when compared with other platinum-containing regimens. [9]

Gemcitabine requires phosphorylation intracellularly to its active form, gemcitabine triphosphate. The rate of this metabolic conversion is limited by the activity of deoxycytidine kinase (DCK). Because this enzyme is saturated at low-dose level, [10],[11] the brief 30-min infusion of gemcitabine at 1000mg/m 2 might not result in higher concentration of its active metabolite. To optimize the saturation of DCK activity, prolonged infusions of gemcitabine, such as the moderately prolonged 100-min infusion (fixed dose rate 10mg/m 2 /min) [12],[13],[14] and the low-dose infusions lasting for 3, 6 or 24 h, [15],[16],[17],[18],[19],[20],[27] have been studied in different clinical trials, and demonstrated good efficacy in different tumors [Table 3]. Among them, the design of low-dose gemcitabine in 6-h prolonged infusion may seem to be more attractive for Chinese patients, possibly due to reducing toxicities and absolutely lowering drug costs. [21]

On the basis of the results of the above trials and possible advantages of low-dose gemcitabine, this study was conducted to evaluate the response rate and toxicity of a 6 h infusion of gemcitabine at a dose of 350mg/m 2 on days 1 and 8 plus carboplatin at 5 AUC on day 1 as first-line chemotherapy for advanced NSCL (stage IIIB and IV).


 » Materials and Methods Top


This study was conducted in patients with advanced NSCLC during the period of January 2009-April 2010. They were followed up till March 2011.

Patient eligibility

  • Patients having histologically or cytologically confirmed NSCLC and inoperable or unresectable stage IIIB (not eligible for curative radiotherapy) and metastatic NSCLC (stage IV).
  • At least one measurable or assessable lesion.
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-2.
  • Acceptable hepatic function [bilirubin <1.5 mg/dl, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) < twice the upper limit of normal] and acceptable renal function (serum creatinine <1.5 mg/dl).


Patients with prior chemotherapy, thoracic radiotherapy, surgery, history of malignancy, brain metastasis, superior venacava syndrome, decompensated cardiac, hepatic, renal or pulmonary disease and HIV positivity were excluded.

Initial evaluation consisted of detailed clinical history, physical examination, biochemical profile, X-ray chest PA view and computed tomography (CT) scan of thorax-upper abdomen. Additional investigations like CT brain, bronchoscopy, bone scan, ultrasound (USG) abdomen were done when clinically indicated.

Patients were divided into two groups as follows.

Arm I: 4-6 cycles of gemcitabine (1000mg/m 2 in 30minutes) on days 1 and 8 plus carboplatin [area under the serum concentration time curve (AUC) 5] given on day 1. Cycle repeated every 3 weekly.

Arm II: 4-6 cycles of prolonged infusion of low-dose gemcitabine (350mg/m 2 in 6 h) on days 1 and 8 plus carboplatin (AUC 5) given on day 1.Cycle repeated every 3 weekly.

Dose modification was done if the absolute neutrophil count (ANC) was less than 1500/μl or the platelet count was less than 75,000/μl on the day of chemotherapy; then chemotherapy was withheld until the counts recovered. If grade 4 hematologic toxicity [Common Toxicity Criteria of the National Cancer Institute (NCI-CTC, Version 2.0)] occurred during the first course, then doses of chemotherapeutic agents were reduced by 25%. Prophylactic growth factor was not used in any patient. A patient who could not be given drug for 30 days from the time of last study drug administration was to be discontinued from the study.

The main end points of trial were response and toxicity. To assess the response and toxicity, all patients underwent complete blood cell count and blood chemistries prior to each chemotherapy cycle during the treatment period. An interim evaluation with CT thorax and upper abdomen was done after two courses of chemotherapy in both arms. For final evaluation, CT thorax plus abdomen was done after completion of 4-6 cycles of chemotherapy in both arms. After completion of four cycles, patients were put on either two more cycles of same chemotherapy or alternative therapy, depending on the response. Thereafter, all the patients were followed up at regular intervals for at least a period of 1 year from the date of diagnosis for survival. Responses were evaluated according to WHO criteria.


 » Results Top


A total of 60 patients were enrolled in this study. Patients' characteristics at baseline are listed in [Table 1]. Histology was predominantly adenocarcinoma (55% of the patients). In the present study, 80% patients were tobacco users and 13.3% patients were addicted to both tobacco and alcohol. All patients were assessable for the safety analysis and response.
Table 1: Patient characteristics

Click here to view


Out of the 60 eligible patients, the ORR was 40% in arm I while it was 36.3% in arm II (P = 0.992, NS). ORR in stage IIIB was 47% in arm I and 40% in arm II, while in stage IV it was 31% in arm I and 33% in arm II. One patient in each arm had complete responses (CRs). 33.3% patients in arm I and 36.6% patients in arm II had stabilization of disease. In both arms, 26.6% patients showed progression of disease [Table 5].

The median time to progressive disease (TTP) was 5.5 months for standard dose arm and 5.4 months for infusional dose arm. Median overall survival (OS) time was 9.7 months for standard dose arm and 10.2 months for infusional dose arm [Figure 1], and 1-year survival was 33.3% for standard dose arm and 36.6% for infusional dose arm.
Figure 1: The Kaplan-Meier curve shows nearly similar survival for the two arms

Click here to view


The grade 3/4 hematologic toxicities [Table 2] were neutropenia in 16.6% and 6.6% patients, thrombocytopenia in 10% and nil, and anemia in 6.6% and 6.6% patients, respectively, in arm I and in arm II. No bleeding episodes were recorded in both arms. No patients required platelet transfusion in both arms and five patients received packed RBC transfusions in arm I, while two patients received packed RBC transfusions in arm II. Nonhematologic toxicity was generally mild [Table 2]. One patient had grade III/IV febrile neutropenia in standard dose arm, while no one had it in low infusional dose arm.
Table 2: Differences in the toxicities among the two arms

Click here to view


A total of 118 chemotherapy cycles, with a median of 4 cycles per patient (range 2-6), and 134 chemotherapy cycles, with a median of 4.47 cycles per patient (range 3-6), were administered in standard and low infusional dose arm, respectively.


 » Discussion Top


Gemcitabine-cisplatin combination has proven to be well tolerated and active, with response rates ranging from 22 to 40.6%, TTP from 4.2 to 6.9 months, median OS from 8.1 to 9.8 months and 1-year survival rate of 32-39% in several large phase III studies. [4],[5],[6],[8] A recent meta-analysis showed an absolute 1-year survival benefit of 3.9% for gemcitabine-cisplatin chemotherapy over other platinum containing regimens. [9] The use of cisplatin or carboplatin as the platinum agent of choice in the treatment of patients with advanced NSCLC remains controversial. Two meta-analyses addressing the question of cisplatin versus carboplatin have yielded conflicting results. [22] The first one, a literature-based analysis that included eight trials and 2948 patients, reported a higher response rate for cisplatin-based chemotherapy (hazard ratio: 1.36; 95% confidence interval: 1.15-1.61; P<0.001), but did not show an improvement in overall survival (hazard ratio: 1.05; 95% confidence interval: 0.91-1.22; P=0.515). There were no differences in treatment-related mortality. [22] The second meta-analysis, which was based on individual patient data and included nine trials with 2968 patients, also reported a higher response rate for cisplatin compared with carboplatin (30% vs. 24%; odds ratio: 1.37; 95% confidence interval: 1.16-1.61; P<0.001). But this analysis also demonstrated improved median and 1-year survival of 9.1 months and 37% for cisplatin and 8.4 months and 34% for carboplatin. [23] In a subset analysis, this difference was significant for patients with nonsquamous histology (hazard ratio: 1.12; 95% confidence interval: 1.01-1.23) and those treated with a third-generation platinum regimen (hazard ratio: 1.11; 95% confidence interval: 1.01-1.21), which comprised 80% of the study population. [23] Treatment toxicities varied by platinum agent as expected; patients who received cisplatin experienced more nausea, vomiting, and renal toxicity, whereas carboplatin-treated patients experienced more thrombocytopenia. [22],[23] The majority of patients with advanced NSCLC have multiple co-morbidities and are often not able to tolerate the cisplatin-based therapy should be considered. Therefore, in the present study, we used carboplatin as a platinum agent. In all the trials, gemcitabine was usually administered in a 30-min infusion on a weekly basis for 2 or 3 weeks. In this study, a 4- to 6-h infusion of gemcitabine at 350mg/m 2 on days 1 and 8 plus carboplatin at AUC 5 was compared with standard dose gemcitabine plus carboplatin (gemcitabine 1000mg/m 2 on days 1 and 8 and carboplatin at AUC 5) in patients with stage IIIB/IV NSCLC, and comparable efficacy was observed.

The most outstanding feature of this schedule, as compared to the standard schedule, was low-dose gemcitabine in prolonged infusion. So far, gemcitabine has been applied in three distinct schedules such as the usual 30-min infusion, the moderately prolonged 100-min infusion (fixed dose rate 10mg/m 2 /min) and the low-dose infusions lasting for 3, 6 or 24 h [Table 4]. The explanation for this phenomenon lies in the saturation of DCK which occurs after short infusion at conventional doses. This enzyme is needed to convert gemcitabine into its active form, gemcitabine triphosphate. While short infusion leaves most of the drug unmetabolized, prolonged infusion results in a higher intracellular concentration of the active metabolite, thus enhancing the agent's efficacy. On the basis of these results, we conducted the present study.
Table 3: Various studies of low infusional dose gemcitabine in other cancers

Click here to view
Table 4: Various studies of low infusional dose gemcitabine in NSCLC

Click here to view
Table 5: Final response evaluation (after six cycles)

Click here to view


At final evaluation in present study, the overall response rate was 40%, survival at 1 year was 33.3% and median OS was 9.7 months with gemcitabine and carboplatin GC (standard dose). While in GC low dose (LD) arm, the overall response rate was 36.6%, survival at 1 year was 36.6% and median OS was 10.2 months.

Parikh et al. [24] reported that complete response was seen in 2 patients, partial response in 36 (50%), stable disease in 22 (30.55%) and progressive disease in 12 (16.66%; 7 cases while on chemotherapy and 5 cases subsequently) patients, giving an overall response of 52.7%.

In the present study, on comparing objective response in two arms, at final evaluation, GC (standard dose) arm showed 3.3% higher response as compared to GC (LD) arm (40% vs. 36.6%), which was not statistically significant (P=0.992). On comparing the survival at 1 year, GC (LD) arm showed 3.3% higher survival as compared to GC (standard dose) arm (36.6% vs. 33.3%), but this was not statistically significant (P=0.78). Median survival of the patients in GC (standard dose) arm was 9.7 months, whereas for GC (LD) arm it was not reached.

In the trial conducted by Zwitter et al., [25] 40 chemonaive patients received gemcitabine at 250mg/m 2 in 6-h infusion on days 1 and 8 plus cisplatin at 75mg/m 2 on day 2 every 3 weeks. Response rate was 45%, median progression-free survival was 6.3 months and median OS was 11.9 months, similar to the present study.

In addition, other trials with gemcitabine at fixed dose rate (10 mg/m 2 /min) plus cisplatin or carboplatin in patients with NSCLC also demonstrated the efficacy of gemcitabine in prolonged infusion [Table 3], with a response rate of 34-41%, median TTP of 5-8 months and OS of 11.5-13 months. Tempero et al. [13] used gemcitabine in a fixed dose rate infusion (10mg/m 2 /min) or standard 30-min infusion for patients with pancreatic carcinoma and observed a longer median survival with the former.

However, with the large dose of gemcitabine unchanged in the fixed dose rate infusions, all the randomized phase II trials [12],[13],[26] indicated hematologic toxicity occurred more in the fixed dose rate arms than in the 30-min infusion arms. In our study, gemcitabine was given at a low-dose level, which presented unexpectedly low hematologic toxicity [Table 2]. No bleeding episodes were recorded in both arms. No patients required platelet transfusion in both arms and five patients received packed RBC transfusions in standard dose arm, while two patients received packed RBC transfusions in low infusional dose arm.

Similarly, in Zwitter et al.'s study, [25] out of 40 patients administered with 6 h infusional gemcitabine at 250mg/ m 2 , 8 patients experienced grade 3/4 neutropenia (20%), coinciding with our report (18.9%). Interestingly, whilethrombocytopenia (grade 3 in one patient) was exceptional, most patients had reversible thrombocytosis with platelets over 500 × 10 9 in 19 (47.5%) patients and over 1000 × 10 9 in 3 (7.5%) patients. In addition, in the rest of 21 patients with doses ranging from 130 to 170, 210mg/m 2 , also 13 patients experienced grade 2 thrombocytosis. In our study, however, none of the patients experienced thrombocytosis. The difference in platelet count was confusing because the same method of administration of gemcitabine was used in these two phase II trials. Is it possibly due to different racial populations? Further studies are needed to confirm the difference or to find out the reason behind it.

As far as nonhematologic toxicity is concerned, similar to Zwitter et al.'s trial and Xiong et al.'s study, nausea and vomiting were most commonly observed, followed by acceptable mucositis, which were comparable to the standard dose arm.

Besides the advantage of much less hematologic toxicity, it also should be noted that lower costs due to low dosing of gemcitabine in this trial made it possible for more patients to continue their chemotherapy. So far, in India at least, drug costs account for the majority of treatment costs for the patients with cancer. A great proportion of patients discontinue their treatment because of failing to afford drug costs rather than intolerable toxicities. Therefore, lowering costs for gemcitabine without lowering its activity is definitely meaningful.

In conclusion, treatment with low-dose gemcitabine in prolonged infusion in combination with carboplatin is feasible. The good efficacy, remarkably mild hematologic toxicity and lower drug costs make it an attractive option for Indian patients with advanced NSCLC, particularly for the elderly or those without good economic condition. This combination deserves to be studied further in comparison with the standard brief infusion of gemcitabine in a randomized trial.

 
 » References Top

1.Le Chevalier T, Brisgand D, Douillard JY, Pujol JL, Alberola V, Monnier A, et al. Randomized study of vinorelbine and cisplatin versus vindesine and cisplatin versus vinorelbine alone in advanced non-small-cell lung cancer: Results of a European multicenter trial including 612 patients. J Clin Oncol 1994;12:360-7.  Back to cited text no. 1
[PUBMED]    
2.Wozniak AJ, Crowley JJ, Balcerzak SP, Weiss GR, Spiridonidis CH, Baker LH, et al. A Southwest Oncology Group study. Randomized trial comparing cisplatin with cisplatin plus vinorelbine in the treatment of advanced non-small cell lung cancer. J Clin Oncol 1998;16:2459-65.  Back to cited text no. 2
[PUBMED]    
3.Bonomi P, Kim K, Fairclough D, Cella D, Kugler J, Rowinsky E, et al. Results of an Eastern Cooperative Oncology Group trial. Comparison of survival and quality of life in advanced non-small-cell lung cancer patients treated with two dose levels of paclitaxel combined with cisplatin versus etoposide with cisplatin. J Clin Oncol 2000;18:623-31.  Back to cited text no. 3
[PUBMED]    
4.Cardenal F, López-Cabrerizo MP, Antón A, Alberola V, Massuti B, Carrato A, et al. Randomized phase III study of gemcitabine-cisplatin versus etoposide-cisplatin in the treatment of locally advanced or metastatic non-small-cell lung cancer. J Clin Oncol 1999;17:12-8.  Back to cited text no. 4
    
5.Scagliotti GV, De Marinis F, Rinaldi M, Crinò L, Gridelli C, Ricci S, et al. Phase III randomized trial comparing three platinum-based doublets in advanced non-small-cell lung cancer Italian Lung Cancer Project. J Clin Oncol 2002;20:4285-91.  Back to cited text no. 5
    
6.Schiller JH, Harrington D, Belani CP, Langer C, Sandler A, Krook J, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med 2002;346:92-8.  Back to cited text no. 6
[PUBMED]    
7.Kelly K, Crowley J, Bunn Jr PA, Presant CA, Grevstad PK. Moinpour non-small-cell lung cancer. J Clin Oncol 2001;19: 3210-8.  Back to cited text no. 7
    
8.Smit EF, Van Meerbeeck JP, Lianes P, Debruyne C, Legrand C, Schramel F, et al. A phase III trial of the European Organization for Research and Treatment of Cancer Lung Cancer Group-EORTC 08975. Three-arm randomized study of two cisplatin based regimens and paclitaxel plus gemcitabine in advanced non-small cell lung cancer. J Clin Oncol 2003;21:3909-17.  Back to cited text no. 8
[PUBMED]    
9.Le Chevalier T, Scagliotti G, Natale R, Danson S, Rosell R, Stahel R, et al. Efficacy of gemcitabine plus platinum chemotherapy compared with other platinum containing regimens in advanced non-small-cell lung cancer: A meta-analysis of survival outcomes. Lung Cancer 2005;47:69-80.  Back to cited text no. 9
[PUBMED]    
10.Plunkett W, Huang P, Xu YZ, Heinemann V, Grunewald R, Gandhi V. Gemcitabine: Metabolism, mechanisms of action and self potentiation. Semin Oncol 1995;22:3-10.  Back to cited text no. 10
    
11.Grunewald R, Kantarjian H, Keating MJ, Abbruzzese J, Tarassoff P, Plunkett W. Pharmacologically directed design of the dose rate and schedule of 2',2'-Difluorodeoxycytidine (Gemcitabine) Administration in Leukemia. Cancer Res 1990;50:6823-6.  Back to cited text no. 11
[PUBMED]    
12.Ceribelli A, Gridelli C, De Marinis F, Fabi A, GCortesi E, Barduagni M, et al. Prolonged gemcitabine infusion in nonsmall cell lung carcinoma: A randomized phase II study of two different schedules in combination with cisplatin. Cancer 2003;98:337-43.  Back to cited text no. 12
    
13.Tempero M, Plunkett W, Ruiz Van Haperen V, Hainsworth J, Hochster H, Lenzi R, et al. Randomized phase II comparison of dose intense Gemcitabine: Thirty-minute infusion and fixed dose rate infusion in patients with pancreatic adenocarcinoma. J Clin Oncol 2003;21:3402-8.  Back to cited text no. 13
[PUBMED]    
14.Xu N, Shen P, Zhang XC, Yu LF, Bao HY, Shi GM, et al. Phase II trial of a 2 h infusion of gemcitabine plus carboplatin as first-line chemotherapy for advanced non-small-cell lung cancer. Cancer Chemother Pharmacol 2007;59:1-7.  Back to cited text no. 14
[PUBMED]    
15.Pollera CF, Ceribelli A, Crecco M, Oliva C, Calabresi F. Prolonged infusion gemcitabine: A clinical phase I study at low- (300mg/m2) and high-dose (875mg/m2) levels. Invest New Drugs 1997;15:115-21.  Back to cited text no. 15
[PUBMED]    
16.Akrivakis K, Schmid P, Flath B, Schweigert M, Sezer O, Mergenthaler HG, et al. Prolonged infusion of gemcitabine in stage IV breast cancer: A phase I study. Anticancer Drugs 1999;10:525-31.  Back to cited text no. 16
[PUBMED]    
17.Schmid P, Akrivakis K, Flath B, Grosse Y, Sezer O, Mergenthaler HG, et al. Phase II trial of gemcitabine as prolonged infusion in metastatic breast cancer. Anticancer Drugs 1999;10:625-31.  Back to cited text no. 17
[PUBMED]    
18.Anderson H, Thatcher N, Walling J, Hansen H. A phase I study of a 24 h infusion of gemcitabine in previously untreated patients with inoperable non-small-cell lung cancer. Br J Cancer 1996;74:460-2.  Back to cited text no. 18
[PUBMED]    
19.Eckel F, Lersch C, Assmann G, Schulte-Frohlinde E. Toxicity of a 24 h infusion of gemcitabine in biliary tract and pancreatic cancer: A pilot study. Cancer Invest 2002;20:180-5.  Back to cited text no. 19
[PUBMED]    
20.Von Delius S, Lersch C, Schulte-frohlinde E, Mayr M, Schmid RM, Eckel F. Phase II trial of weekly 24 h infusion of gemcitabine in patients with advanced gallbladder and biliary tract carcinoma. BMC Cancer 2005;5:61.  Back to cited text no. 20
[PUBMED]    
21.Xiong JP, Feng M, Qiu F, Xu J, Tao QS, Zhang L, et al. Phase II trial of low-dose gemcitabine in prolonged infusion and cisplatin for advanced non-small cell lung cancer. Lung Cancer 2008;60:208-14.  Back to cited text no. 21
[PUBMED]    
22.Hotta K, Matsuo K, Ueoka H, Kiura K, Tabata M, Tanimoto M. Meta-analysis of randomized clinical trials comparing cisplatin to carboplatin in patients with advanced non-small-cell lung cancer. J Clin Oncol 2004;22:3852-9.  Back to cited text no. 22
[PUBMED]    
23.Ardizzoni A, Boni L, Tiseo M, Fossella FV, Schiller JH, Paesmans M, et al. Cisplatin- vs carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: An individual patient data meta-analysis. J Natl Cancer Inst 2007;99:847-57.  Back to cited text no. 23
[PUBMED]    
24.Parikh PM, Narayanan P, Mistry RC, Agarwal J P, Pai VR, Nair R, et al. Treatment of advanced NSCLC (Stage IIIB and IV) with low dose gemcitabine and carboplatin. J Clin Oncol 2005;23:16_suppl 7306.  Back to cited text no. 24
    
25.Zwitter M, Kovac V, Smrdel U, Kocijancic I, Segedin B, Vrankar M. Phase I-II trial of low-dose gemcitabine in prolonged infusion and cisplatin for advanced non-small cell lung cancer. Anticancer Drugs 2005;16:1129-34.  Back to cited text no. 25
[PUBMED]    
26.Cappuzzo F, Novello S, De Marinis F, Selvaggi G, Scagliotti GV, Barbieri F, et al. A randomized phase II trial evaluating standard (50mg/min) versus low (10mg/min) infusion duration of gemcitabine as first-line treatment in advanced non-small-cell lung cancer patients who are not eligible for platinum-based chemotherapy. Lung Cancer 2006;52:319-25.  Back to cited text no. 26
    
27.Maurel J, Zorrilla M, Puertolas T, Antón A, Herrero A, Artal A, et al. Phase I trial of weekly gemcitabine at 3 h infusion in refractory, heavily pretreated advanced solid tumors. Anticancer Drugs 2001;12:713-7.  Back to cited text no. 27
    


    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]

This article has been cited by
1 Phase III Non-inferiority Study Evaluating Efficacy and Safety of Low Dose Gemcitabine Compared to Standard Dose Gemcitabine With Platinum in Advanced Squamous Lung Cancer
Vijay Patil,Vanita Noronha,Amit Joshi,Anuradha Chougule,Sadhana Kannan,Atanu Bhattacharjee,Supriya Goud,Sucheta More,Arun Chandrasekharan,Nandini Menon,Sujay Srinivas,Dilip Harindran Vallathol,Hollis Dsouza,Swaratika Majumdar,Sudeep Das,Abhinav Zawar,Satvik Khaddar,Amit Kumar,Gunjesh Singh,Kanteti Aditya Pavan Kumar,Rahul Ravind,Vaishakhi Trivedi,Vichitra Behel,Abhishek Mahajan,Amit Janu,Nilendu Purandare,Kumar Prabhash
EClinicalMedicine. 2019; 9: 19
[Pubmed] | [DOI]
2 Meta-analysis of gemcitabine in brief versus prolonged low-dose infusion for advanced non-small cell lung cancer
Zhao Dehua,Chu Mingming,Wang Jisheng,Christina L. Addison
PLOS ONE. 2018; 13(3): e0193814
[Pubmed] | [DOI]
3 Gemcitabine-(5'-phosphoramidate)-[anti-IGF-1R]: molecular design, synthetic organic chemistry reactions, and antineoplastic cytotoxic potency in populations of pulmonary adenocarcinoma (A549)
Cody P. Coyne,Lakshmi Narayanan
Chemical Biology & Drug Design. 2017; 89(3): 379
[Pubmed] | [DOI]
4 Combination of low-dose gemcitabine in 6-hour infusion and carboplatin is a favorable option for patients in poor performance status with advanced non-small cell lung cancer
Zhi-Yong Wu,Hui-Hong Guan,Ze-Xiao Lin,Hong-Kai Yang,Lan Zhou,Qi-Chun Cai
Journal of Chemotherapy. 2014; 26(5): 306
[Pubmed] | [DOI]
5 Low-dose gemcitabine in long infusion: When less is more
Zwitter, M.
Indian Journal of Cancer. 2012; 49(2): 199-201
[Pubmed]
6 Optimizing patient outcome: Of equal importance in the palliative setting
Parikh, P. and Narayanan, P. and Bhattacharyya, Gs.
Indian Journal of Cancer. 2012; 49(3): 255-259
[Pubmed]



 

Top
Print this article  Email this article
 

    

  Site Map | What's new | Copyright and Disclaimer
  Online since 1st April '07
  © 2007 - Indian Journal of Cancer | Published by Wolters Kluwer - Medknow