|Year : 2017 | Volume
| Issue : 1 | Page : 169-171
Gemcitabine and carboplatin in metastatic nonsmall cell lung cancer: Experience from a tertiary cancer center in South India
T Devika1, B Dubashi2, DG Shewade1, S Kayal2, RCS Kumar2
1 Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
2 Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
|Date of Web Publication||1-Dec-2017|
Dr. B Dubashi
Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry
Source of Support: None, Conflict of Interest: None
BACKGROUND: Gemcitabine and carboplatin combination is widely used as one of the first-line chemotherapeutic regimens in patients with metastatic nonsmall cell lung cancer patients. METHODOLOGY: A total of 112 patients with metastatic disease were recruited. They were on standard 21-day gemcitabine 1.2 g/m2 and carboplatin AUC 5 dosing schedule. Each patient received at least four cycles and a maximum of 6 cycles of treatment. The patients were followed up, and the demographic, efficacy and toxicity profiles were analyzed. RESULT: The mean age was 53.81±9.85 with 71 male and 41 female patients. Response assessment was done in 82 patients, and the objective response rate was found to be 47.6% with 39 partial responders, 20 patients with stable disease and 23 patients with progressive disease. The median overall survival was 12 months (95% CI 9.89-14.11). We found anemia (62.5%) to be more prominent than the other toxicities followed by thrombocytopenia and vomiting (31.3%). The nonhematological toxicities were minimal and manageable. CONCLUSION: Treatment with gemcitabine and carboplatin is efficacious with manageable toxicity profile in the real world non-clinical trial setting.
Keywords: Chemotherapy, gemcitabine and carboplatin, metastatic lung cancer
|How to cite this article:|
Devika T, Dubashi B, Shewade D G, Kayal S, Kumar R. Gemcitabine and carboplatin in metastatic nonsmall cell lung cancer: Experience from a tertiary cancer center in South India. Indian J Cancer 2017;54:169-71
|How to cite this URL:|
Devika T, Dubashi B, Shewade D G, Kayal S, Kumar R. Gemcitabine and carboplatin in metastatic nonsmall cell lung cancer: Experience from a tertiary cancer center in South India. Indian J Cancer [serial online] 2017 [cited 2020 Feb 25];54:169-71. Available from: http://www.indianjcancer.com/text.asp?2017/54/1/169/219574
| » Introduction|| |
Lung cancer is one of the most common cancers worldwide. Gemcitabine-based regimens are widely used in the treatment of metastatic lung cancer. According to GLOBOCAN, it was estimated that there were 1.8 million new cases in 2012 (12.9% of the total) of which, 58% occurred in less developed regions. Around 85% of lung cancers are nonsmall cell lung cancer (NSCLC) and most of the patients present with metastatic disease, making it difficult in deciding the other therapeutic options such as surgery and radiation. Chemotherapy remains the major component of standard and supportive care in these patients. Gemcitabine and carboplatin is one of the first-line chemotherapy in advanced NSCLC. Gemcitabine is a deoxycytidine analog that is used in the treatment of cancers, including pancreatic, lung, and breast cancer. It has shown efficacy both as a single agent and in combination with other chemotherapeutic drugs., Gemcitabine and carboplatin combination regimen offers significant response (29.6% vs. 11.3%) and survival benefits (2 year survival rate 15% vs. 5%) compared to gemcitabine alone with high but manageable hematological toxicities. Meta-analyses comparing the efficacy has proved that platinum-based combination regimens have significant response  and survival benefits. Nevertheless, the toxicity with carboplatin is higher compared to the other nonplatinum regimens with similar efficacy. However, there are no standard regimen guidelines available for the treatment of NSCLC. Most of the combinations show similar efficacy and survival outcomes., We present the efficacy, survival and toxicity profiles of metastatic lung cancer patients on gemcitabine and carboplatin regimen from a tertiary hospital.
| » Methodology|| |
The study participants from the outpatient department of regional cancer center were recruited from July 2014 to May 2016. The Performance Status (PS) of the patients was evaluated using the scale, Eastern Cooperative Oncology Group-PS (ECOG-PS). Patients diagnosed with metastatic lung cancer who received gemcitabine and carboplatin as first-line chemotherapy were enrolled after meeting the inclusion criteria of age between 18 and 65 years with no organ dysfunction and ECOG-PS ≤2. Exclusion criteria include pregnant and lactating women, patients with renal and liver dysfunction (serum creatinine ≥1.5 and serum transaminase ≥2 times the normal value). Before the start of chemotherapy prechemotherapy investigations and baseline computed tomography (CT) scan was performed for organ functional status. Patients were treated with 1200 mg/m 2 of gemcitabine on day 1 and day 8, carboplatin of area under the curve 5 was given in addition on day 1. The treatment was repeated every 3 weeks. A maximum of six cycles were administered. At the end of chemotherapy, CT scan was done and compared with the baseline CT for response evaluation. The response assessment was performed according to the RECIST guidelines. Toxicity data were collected and graded according to Common Terminology Criteria for Adverse Events version 4.03. All the patients were analyzed for the demographic profile, efficacy, and survival outcomes. Statistical analysis was performed using the statistical software, SPSS version 16.0 (IBM PASW Statistics version 9.0).
| » Results|| |
One hundred and twelve lung cancer patients were enrolled during the study. The mean age was 53.81 ± 9.85 with 71 male and 41 female patients. Histological subtypes include adenocarcinoma (n = 72), adenosquamous (n = 4), squamous (n = 10), undifferentiated (n = 26). Forty-seven of patients were smokers, and 23 patients had a history of alcohol consumption. Patients with ECOG-PS of 1 include n = 67, with ECOG-PS 2 include n = 45. EGFR status was evaluable for 26 patients of which 16 patients were positive for EGFR mutation, and 10 patients were found to be negative and in 85 patients it was unknown.
The median number of chemotherapy cycles was 4 (1-6). Response was evaluable for 82 patients, of which we did not find any patients with complete response. Partial response (PR) was observed in 39 patients, stable disease (SD), n = 20, and progressive disease (PD) was observed in 23 patients [Table 1]. The objective response rate was 47.6% (PR), and the nonresponders include 52.4% (SD and PD). Survival analysis was performed, and the median overall survival was found to be 12 months (95% confidence interval = 9.89–14.11).
|Table 1: Baseline characteristics of metastatic nonsmall cell lung cancer patients|
Click here to view
Toxicity profile was evaluated for 112 patients. They were categorized into hematological and nonhematological toxicities [Table 2]. The nonhematological toxicities were mild and they were manageable. Among hematological toxicities, anemia (62.5%) was found to be higher followed by thrombocytopenia (31.3%). Few patients underwent blood transfusion and Granulocyte-colony stimulating factor injection administration. Dose adjustments and delay in consecutive chemotherapy cycles were made according to hematological recovery.
|Table 2: Toxicity profile based on Common Terminology Criteria for Adverse Events guidelines|
Click here to view
| » Discussion|| |
The objective response rate is higher in this study than Obasaju et al. with the 21-day schedule regimen, whereas the median overall survival was consistent. In a recent study on elderly NSCLC patients with survival outcome as the primary objective, the median survival was slightly higher (14.9 mo) when compared with the present study. Results from a study by London lung cancer group were comparable with the present study. The objective response rate and survival were almost similar, whereas the toxicity profiles differed significantly and was found to be lower in the present study.
The hematological toxicities were more prominent compared to other toxicities, which is in agreement with the toxicity data available in the literature for gemcitabine and carboplatin. Grade III and IV hematological toxicities were observed in lesser percentage of patients in this study when compared to Grønberg et al. In a randomized Phase III multicenter clinical trial with 1135 patients, survival and response rates are lower, whereas the hematological and nonhematological toxicities of Grades III and IV are high compared to this study. Another randomized clinical trial observed a higher percentage of neutropenia and thrombocytopenia, whereas Grade III and Grade IV anemia is found in a higher rate (17.9% and 5.4%) in the present study. However, the proportion of Grade III and Grade IV nonhematological toxicities such as vomiting, diarrhea, and myalgia are slightly higher in the present study. A clinical study administered alternate carboplatin and gemcitabine dosing schedule on 36 patients showed lower response and survival rates and higher toxicities compared to the our study. The differences in toxicities and efficacy profiles may also be due to differences in the population size between the studies which cannot be ruled out.
| » Conclusion|| |
We present the demographic, efficacy, and toxicity profiles of NSCLC patients on gemcitabine and carboplatin doublet regimen from a tertiary care center. Treatment with this regimen is efficacious with manageable toxicity profile in a real world nonclinical trial setting.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| » References|| |
Pfister DG, Johnson DH, Azzoli CG, Sause W, Smith TJ, Baker S Jr., et al.
American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: Update 2003. J Clin Oncol 2004;22:330-53.
Toschi L, Finocchiaro G, Bartolini S, Gioia V, Cappuzzo F. Role of gemcitabine in cancer therapy. Future Oncol 2005;1:7-17.
Metro G, Cappuzzo F, Finocchiaro G, Toschi L, Crinò L. Development of gemcitabine in non-small cell lung cancer: The Italian contribution. Ann Oncol 2006;17 Suppl 5:v37-46.
Sederholm C, Hillerdal G, Lamberg K, Kölbeck K, Dufmats M, Westberg R, et al.
Phase III trial of gemcitabine plus carboplatin versus single-agent gemcitabine in the treatment of locally advanced or metastatic non-small-cell lung cancer: The Swedish Lung Cancer Study Group. J Clin Oncol 2005;23:8380-8.
D'Addario G, Pintilie M, Leighl NB, Feld R, Cerny T, Shepherd FA. Platinum-based versus non-platinum-based chemotherapy in advanced non-small-cell lung cancer: A meta-analysis of the published literature. J Clin Oncol 2005;23:2926-36.
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.
Li C, Sun Y, Pan Y, Wang Q, Yang S, Chen H. Gemcitabine plus paclitaxel versus carboplatin plus either gemcitabine or paclitaxel in advanced non-small-cell lung cancer: A literature-based meta-analysis. Lung 2010;188:359-64.
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.
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. J Clin Oncol 2002;20:4285-91.
Obasaju CK, Ye Z, Bloss LP, Monberg MJ, Curiel RE. Gemcitabine/carboplatin in patients with metastatic non-small-cell lung cancer: Phase II study of 28-day and 21-day schedules. Clin Lung Cancer 2005;7:202-7.
Fantini M, Stocchi L, Affatato A, Papi M, Sartori S, Ioli G, et al
. Carboplatin-gemcitabine in the treatment of elderly patients with non-small cell lung cancer: An outcome analysis. J Cancer Res Ther 2015;3:112-7.
Rudd RM, Gower NH, Spiro SG, Eisen TG, Harper PG, Littler JA, et al.
Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV non-small-cell lung cancer: A phase III randomized study of the London Lung Cancer Group. J Clin Oncol 2005;23:142-53.
Grønberg BH, Bremnes RM, Fløtten O, Amundsen T, Brunsvig PF, Hjelde HH, et al.
Phase III study by the Norwegian lung cancer study group: Pemetrexed plus carboplatin compared with gemcitabine plus carboplatin as first-line chemotherapy in advanced non-small-cell lung cancer. J Clin Oncol 2009;27:3217-24.
Treat JA, Gonin R, Socinski MA, Edelman MJ, Catalano RB, Marinucci DM, et al.
Arandomized, phase III multicenter trial of gemcitabine in combination with carboplatin or paclitaxel versus paclitaxel plus carboplatin in patients with advanced or metastatic non-small-cell lung cancer. Ann Oncol 2010;21:540-7.
Fidias PM, Dakhil SR, Lyss AP, Loesch DM, Waterhouse DM, Bromund JL, et al.
Phase III study of immediate compared with delayed docetaxel after front-line therapy with gemcitabine plus carboplatin in advanced non-small-cell lung cancer. J Clin Oncol 2009;27:591-8.
Mott FE, Cable CT, Sharma N. Phase II study of an alternate carboplatin and gemcitabine dosing schedule in advanced non-small-cell lung cancer. Clin Lung Cancer 2003;5:174-6.
[Table 1], [Table 2]