Although platinum based chemotherapy is known to improve the survival duration for the patients with non-small cell lung cancer, the role of platinum for elderly patient is not yet clear. We administered gemcitabine and carboplatin combination therapy to elderly patients with NSCLC. The aim of this study was to evaluate the efficacy and toxicities of this regimen for elderly patients.
The eligibility criteria were as follows: pathologically confirmed NSCLC, an age ≥65 years, advanced disease with stage IIIB or IV and the patients were chemotherapy-naive. The treatment regimen was as follows; gemcitabine 1,000 mg/m2 was administered on days 1 and 8 and carboplatin AUC=5 was administered on day 1. This regimen was repeated every 3 weeks. The efficacy was evaluated in terms of the response rate, the time to progression and the overall survival duration.
From Dec 2001 to Feb 2005, a total of 20 patients were entered into this study. The median patient age was 68 years (range: 65~75). 19 patients were evaluable for their treatment response. A partial response was obtained in 8 patients (response rate: 42.1%, 95% CI: 19.4~64.8%). The median time to progression and the survival duration were 136 days and 453 days, respectively. Among a total of 65 cycles of treatment, grade 3 or 4 leukopenia and thrombocytopenia were observed in 7.7% and 13.9% of the cycles, respectively. Grade 3 or 4 vomiting was observed in 7.7% of the cycles. Grade 3 skin rash developed in 1.5% of the cycles. 1 patient died of septic shock after chemotherapy.
Gemcitabine and carboplatin combination chemotherapy was relatively safe and effective for treating elderly patients with NSCLC.
Lung cancer is the leading cause of cancer death in most countries (
A meta-analysis revealed that patients with advanced non-small cell lung cancer (NSCLC) and who were treated with platinum-containing chemotherapy regimens had a 10% improvement of their 1 year survival compared with those who were managed with supportive care only (
Some reports have recently clarified the benefit of chemotherapy for elderly patients. A randomized trial of vinorelbine versus the best supportive care for patients 70 years of age or older demonstrated a definite improvement in the overall survival rate and quality of life with administering chemotherapy (
Nevertheless, the most appropriate regimen for elderly patients with NSCLC has not yet been established. The exact role of platinum compounds and combination chemotherapy for elderly patient is still being debated.
Gemcitabine is active against NSCLC and it is well tolerated too. Gemcitabine monotherapy in elderly patients with NSCLC produced an overall response rate of 22.2~38.5% with minimal toxicities (
Platinum combination chemotherapy is considered as a standard therapy for patients with NSCLC. However, many medical oncologists often hesitate to add cisplatin to treat elderly patients because of the concern about excessive toxicities.
Carboplatin is less toxic than cisplatin and it has been demonstrated to be just as efficacious for the treatment of NSCLC (
There are various doses and schedules for gemcitabine and carboplatin combination therapy. However, the efficacy and toxicity seem to be similar among the various methods (
On the basis of these considerations, we administered gemcitabine and carboplatin combination therapy to elderly Korean patients with NSCLC, and we report here on the results.
The patients with an age ≥65 had to fulfill all the following criteria to be eligible for this study: have a histologically or cytologically proven NSCLC, have stage IIIB or IV disease that wasn't suitable for curative resection or recurred disease after resection, have measurable lesions and a good performance status (ECOG 0~2), have no experience of previous chemotherapy with or without a previous history of radiotherapy history, have adequate bone marrow (granulocyte ≥1,800/mm3, platelet ≥100,000/mm3), hepatic (total bilirubin ≤2.0 mg/dL) and, renal (creatinine clearance ≥50 mL/min) functions. An informed written consent was obtained from all the patients who were entered into this study.
Gemcitabine was administrated at a dose of 1,000 mg/m2 on days 1 and 8. Carboplatin was administered at a dose of AUC=5 on day 1. The dose of carboplatin was calculated according to the Calvert formula. This combined regimen was repeated every 3 weeks.
The dose of gemcitabine on day 8 was modified as follows according to the CBC. It was reduced to 50% of the planned dose if the granulocyte count was 500 to 999/mm3 and/or the platelet count was 50,000 to 74,900/mm3. The administration of gemcitabine was omitted if the granulocyte count was below 500/mm3 or the platelet count was below 50,000/mm3.
This treatment was repeated until disease progression or the appearance of unacceptable toxicities or until a maximum 4 cycles. After the planned treatment, further treatment with this protocol or second line treatment were performed based on the physician's choice.
A CBC, blood chemistry tests, chest X-rays and physical exam were repeated before every chemotherapy cycle. The follow-up studies with computerized tomography and bone scanning were performed every 2 cycles of chemotherapy. The responses were classified according to the World Health Organization criteria. Treatment toxicities were evaluated according to the National Cancer Institute Common Toxicity Criteria version 3.0.
The primary object of this study was response rate. The secondary endpoints were the overall survival duration, the time to progression and the toxicities of this regimen. The overall survival duration is defined as the time between the date of starting treatment and the last date that the patient was known to be alive. Progression free survival is defined as the time from the date of starting treatment to disease progression or to death from disease progression or unknown causes. Both overall survival and the time to progression were calculated using the Kaplan-Meier method. The Medcalc program version 8.0 was used for statistical analysis.
From Dec 2001 to Feb 2005, a total of 20 patients were entered into this study. Thirteen (65%) patients were male and seven (35%) were female. Three patients (15%) had stage IIIB disease and 17 (85%) had stage IV disease. The performance status was 6 (30%), 12 (60%) and 2 (10%) patients in ECOG 0, 1 and 2, respectively. Eight patients (40%) were (70 years of age and the median patient age was 68 years (range: 65~75). The patients' characteristics are summarized on
Twenty patients received a total of 65 cycles of chemotherapy. The patients received 1~6 cycles of treatment (median: 4 cycles). Twelve patients (60% of the total patients) fulfilled the planned therapy of 4 or more cycles (6 patients were aged less than 70 and 6 patients were aged 70 or more). The number of cycles of chemotherapy received was not significantly different between these two age groups (p=0.225). Among the total 65 cycles of therapy, the dose at day 8 was reduced in 10 cycles (15.4%).
Among the total 20 patients, 19 patients were evaluable for their treatment response, except the 1 case of early death. There was no complete remission. Partial remissions were observed in 8 patients among the total 19 patients (42.1%). So, the overall response rate was 42.1% (95% C.I.: 19.4~64.8%). The responses after treatment are summarized in
The median time to progression was 136 days (
Toxicities were evaluated for a total 65 cycles of treatment. One patient aged 67 years died of pneumonia and the consequent septic shock without neutropenia after 1 cycle of chemotherapy. This patient experienced severe nausea and vomiting after chemotherapy, and the suspected cause of the pneumonia was aspiration during vomiting.
The grade 3 or 4 hematologic and non-hematologic toxicities are presented in
12 patients among the total 20 patients received second line treatment after failure with gemcitabine and carboplatin combination chemotherapy. Most of them (11 of 12) were treated with a docetaxel-based regimen. 1 patient was treated with gefitinib.
For the patients with NSCLC, the 3rd generation platinum-based regimens yield similar results in terms of the response rate and the overall survival duration. All of the 3rd generation platinum-based regimens are now considered as standard regimens for NSCLC (
In this study, the response rate of 42.1% is comparable to the reports that included younger age patients (
There were some differences in study design between this study and the ELVIS trial. Most importantly, we defined the elderly group as patients aged 65 or more, while the ELIVS trial included only patients aged 70 or more. There is currently no consensus upon the definition of an elderly patient Some authors have enrolled patients aged 65 or more in their study for elderly patients (
For the aspect of the toxicity profile, this regimen was well-tolerated with only rare grade 3 or 4 hematologic and non-hematologic toxicities. However, two patients refused further treatment after 2 cycles of treatment. This seems to be caused by the attitude of the elderly patients and their family members toward the medical treatment. They were not willing to endure the toxicities and they too easily gave up on further treatment. The clinical benefit of chemotherapy for elderly patients has been displayed by many reports (
The toxicities of chemotherapy may depend on the race of the patients. Traditionally, the Japanese treat their patients with less intensive doses of chemotherapy in the belief that an Asian cannot tolerate the dose that's defined for the Caucasian (
Gemciatine and carboplatin combination chemotherapy was tolerated and effective for elderly patients with NSCLC.
This work was supported by a 2003
Time to progression.
Overall survival.
Patient's characteristics
Responses after treatment
Toxicities (% of cycles) in total 65 cycles of treatment