Triplet chemotherapy with cisplatin, gemcitabine and vinorelbine for malignant pleural mesothelioma

BACKGROUND: The incidence of malignant pleural mesothelioma (MPM) is expected to increase due to delayed control of occupational exposure to asbestos in Japan. We investigated the use of triplet combination chemotherapy with cisplatin (CDDP), gemcitabine (GEM) and vinorelbine (VNR) for the treatment of Japanese patients with MPM. METHODS: From December 2000 to August 2003, 12 patients received the following regimen: CDDP 40 mg/m(2), GEM 800 mg/m(2) and VNR 20 mg/m(2) on days 1 and 8 every 4 weeks. Among the 12 patients, six selected patients underwent an extrapleural pneumonectomy (EP) after a median of three cycles of triplet chemotherapy. RESULTS: The overall response rate for all patients and the response rate for chemotherapy-naive cases were 58 and 67%, respectively. The median survival time and survival rate at 2 years for all patients were 11 months and 50%, respectively. The 2-year survival rates for the patients with and without EP were 83.3 and 16.7%, respectively. CONCLUSIONS: Triplet chemotherapy with CDDP, GEM and VNR was thus found to be highly effective for patients with MPM and its toxicity was manageable. A multi-institutional phase II trial is now being planned to establish the effectiveness of this new regimen in chemotherapy-naive patients with MPM.     

JCOG trials of systemic chemotherapy for unresectable or recurrent gastric cancer

From the late 1980s to the early 1990s, the Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group (GIOSG/JCOG) conducted several phase II studies, some of which evaluated oral fluoropyrimidines and others of which introduced Western regimens to Japanese patients. Thereafter, in the phase III study JOCG9205 comparing 5-fluorouracil (5-FU), 5-FU plus cisplatin (CDDP) (FP), and uracil and tegafur (UFT) plus mitomycin (UFTM), neither FP nor UFTM showed a survival benefit over 5-FU alone. Whereas irinotecan (CPT-11) and S-1 (new oral fluoropyrimidine) were developed with promising action against gastric cancer in the late 1990s, these agents cannot be used for patients with impaired oral intake and bowel passage caused by severe peritoneal metastasis. Sequential methotrexate (MTX) and 5-FU (MF) therapy showed substantial action against peritoneal metastasis. Thus, GIOSG/JCOG followed different treatment strategies according to the presence or absence of severe peritoneal metastasis. The phase III study JCOG9912, comparing 5-FU, CPT-11 plus CDDP, and S-1, showed a highly significant noninferiority of S-1 to 5-FU in overall survival associated with acceptable toxicities and concluded that S-1 should be considered for the standard chemotherapy for gastric cancer without severe peritoneal metastasis. For patients with severe peritoneal metastasis, the phase III study JCOG0106 compares MF to 5-FU. In that study, patient enrollment has been completed and a final analysis is planned at the end of 2008. The randomized phase II study JCOG0407 compares the best available 5-FU with weekly paclitaxel after failure in first-line chemotherapy containing 5-FU.     

Functional polymorphisms of the microsomal epoxide hydrolase gene: a reappraisal on a early-onset lung cancer patients series

As concomitant chemoradiotherapy for stage III NSCLC is associated with survival advantage in comparison to a sequential approach, we conducted a phase III randomised study aiming to determine the best sequence and safety of chemotherapy (CT) and chemoradiotherapy (CT-RT), using a regimen with cisplatin (CDDP), gemcitabine (GEM) and vinorelbine (VNR). Unresectable stage III NSCLC patients received CDDP (60 mg/m(2)), GEM (1g/m(2), days 1 and 8) and VNR (25mg/m(2), days 1 and 8) with reduced dosage of GEM and VNR during radiotherapy (66Gy). Two cycles of CT with radiotherapy followed by two further cycles of CT alone were administered in arm A or the reverse sequence in arm B. The study was prematurely closed for poor accrual due to administrative problems. Forty-nine eligible patients were randomised. Response rates and median survival times were, respectively 57% (95% CI: 36-78%) and 17 months (95% CI: 9.3-24.6 months) in arm A and 79% (95% CI: 64-94%) and 23.9 months (95% CI: 13.3-34.5 months) in arm B (p>0.05). Chemotherapy dose-intensity was significantly reduced in arm A. Grade 3-4 oesophagitis occurred in 5 patients. One case of grade 5 radiation pneumonitis was observed. In conclusion, chemoradiotherapy with CDDP, GEM and VNR appears feasible as initial treatment or after induction chemotherapy. Consolidation chemoradiotherapy seems less toxic with a better observed response rates and survival although no valid conclusion can be drawn from the comparison of both arms.     

Chemotherapy for metastatic disease: review from JCOG trials

The Gastrointestinal Oncology Study Group of Japan Clinical Oncology Group (GIOSG/JCOG) has conducted several clinical trials to establish standard chemotherapy for unresectable or recurrent gastric cancer. From the late 1980s to early 1990s, two phase II studies by JCOG evaluated oral fluoropyrimidines, and others introduced Western chemotherapy regimens. Thereafter, the first phase III study (JCOG9205), comparing 5-fluorouracil (5-FU), 5-FU plus ciplatin (CDDP) (FP), and uracil and tegafur (UFT) plus mitomycin (UFTM), could not show a survival benefit of either FP or UFTM over 5-FU alone. In the late 1990s, new active agents such as irinotecan (CPT-11) and S-1 (new oral fluoropyrimidine) showed promising results in their phase II trials. The latest phase III study (JCOG9912), comparing 5-FU, CPT-11 plus CDDP, and S-1, showed significant noninferiority of S-1 to 5-FU in overall survival, associated with a better response rate and progression-free survival and acceptable toxicities, and concluded that S-1 should be considered for the standard chemotherapy of unresectable or recurrent gastric cancer. Simultaneously, another Japanese phase III trial comparing S-1 with S-1 plus CDDP showed a survival benefit of S-1 plus CDDP. At present, S-1 plus CDDP is recognized as standard chemotherapy for unresectable or recurrent gastric cancer, and new treatment with molecular target agents is under development.     

Pemetrexed in the treatment of advanced non-small-cell lung cancer: a review of the clinical data

Pemetrexed is a novel multitargeting antimetabolite that has first-line and second-line activity against non-small cell lung cancer (NSCLC). Phase II studies have shown significant efficacy and a favorable toxicity profile of the combination of pemetrexed plus platinum as first-line therapy for NSCLC. Second-line activity against NSCLC was demonstrated in a phase III trial comparing single-agent pemetrexed with docetaxel; in that trial, survival was comparable between these agents but side effects were significantly less for patients who received pemetrexed. Pemetrexed is also an active agent against mesothelioma. A phase III trial comparing pemetrexed plus cisplatin with cisplatin alone showed for the first time a regimen that improves survival in this disease and led to FDA approval of pemetrexed in combination with cisplatin for mesothelioma. As a radiosensitizer, pemetrexed has been well-tolerated when given concurrent with chest radiation, and a phase I study is under way assessing its tolerability in combination with carboplatin in this setting. Pemetrexed is clearly a useful agent in the treatment of thoracic malignancies, and is worthy of further study in combination with other drugs having novel mechanisms of action.     

Two cases of advanced biliary tract cancer successfully treated with gemcitabine combination chemotherapy

Case 1: A man in his sixties underwent extended right lobectomy of the liver for hepatic hilar cholangiocarcinoma (stage III, fCur B)in July2002. CT scans revealed cancerous pleuritis in March 2005, and he was treated with the chemotherapy of GEM alone as first-line, combined chemotherapy of S-1 and GEM as second-line, and CDDP and GEM as third-line treatment. These therapies have been effective for about 20 months. Case 2: A woman in her sixties was diagnosed with advanced gallbladder cancer(stage IVb)in September 2005. She was given combined chemotherapy of S-1+GEM as first-line, and CDDP+GEM as second-line treatment. The main tumor and metastatic lymph nodes were shrunk, allowing us to perform extended hepatectomy. Histopathologic examinations of the resected specimen of the liver involved by the tumor showed the increased infiltration of inflammatorycells and fibrosis. These patients have been managed on an outpatient basis with good QOL and cancer controlled. Although there has been no established standard regimen, the combined chemotherapy based on GEM will be a provisional standard regimen for patients with advanced biliarytract cancers.     

A case of malignant peritoneal mesothelioma successfully treated with carboplatin and paclitaxel

A 71-year-old woman was seen at our hospital because of abdominal fullness and dyspnea. Examinations revealed a tumor in the pelvis with fluid collection and dissemination was seen in the abdomen and chest. Moreover, hyaluronate in ascites rose to 20,000 mg/dl. Finally, by cytology of ascites using immunohistochemistry, the patient was diagnosed as malignant peritoneal mesothelioma with disseminations in the abdomen and chest. After intraperitoneal administration of 25 mg of cisplatin (CDDP), we started carboplatin (CBDCA) plus paclitaxel (PTX) combination chemotherapy (each treatment course consisted of 100 mg of PTX and 400 mg of CBDCA on day 1 and PTX 100 mg on day 8 and day 15 by intravenous administration followed by 2 drug-free weeks). After the sixth course, a complete remission was observed. Malignant mesothelioma is known to have a poor prognosis. However, we successfully treated malignant peritoneal mesothelioma with CBDCA and PTX combined chemotherapy. Our case suggests that we could improve the prognosis of malignant mesothelioma by aggressive chemotherapy.     

Gemcitabine improved QOL and survival in a case of diffuse malignant pleural mesothelioma

Diffuse malignant pleural mesothelioma is a disease with poor prognosis, and no standard therapy for inoperable cases has been established. There are several reported trials using various anticancer drugs, but their sample sizes were small and none documented the drugs' effectiveness. Recently, some reports revealed that gemcitabine (GEM), which has been demonstrated to be effective for the treatment of non-small cell lung carcinoma, was effective in cases of diffuse malignant pleural mesothelioma. We also treated a 76-year-old female patient with inoperable, biphasic malignant pleural mesothelioma in whom monotherapy with GEM 1,000 mg/m2 was continued leading to improved QOL and survival for 2 years. Though diagnostic imaging indicated SD (stable disease), a high efficacy was observed in terms of reduced subjective symptoms such as a feeling of difficulty in breathing and pain. It is suggested that GEM is a potentially effective drug for the improvement of QOL in inoperable cases of diffuse malignant pleural mesothelioma.     

The emerging role of antifolates in the treatment of malignant pleural mesothelioma

Clinicians have long regarded malignant pleural mesothelioma as a chemoresistant neoplasm and as a result no standard chemotherapy regimen has emerged. Antifolates such as methotrexate are among the most active compounds in mesothelioma, albeit based only on phase II data. Recently two antifolate-based combinations with apparently higher efficacy than older regimens have emerged: the pemetrexed/cisplatin regimen and the raltitrexed/oxaliplatin regimen. In two phase I trials with pemetrexed combined with either cisplatin or carboplatin responses occurred in five of 11 and nine of 29 patients, respectively. In a phase I trial of raltitrexed/oxaliplatin, six of 17 patients (35%) with mesothelioma achieved a partial response. In a phase II trial of raltitrexed/oxaliplatin, 14 objective responses were confirmed in 72 patients (25%) with malignant pleural mesothelioma. Indeed, responses were seen in cisplatin-refractory patients. Based on the promising results from these combination trials, two large phase III studies have begun. The first study was a multicenter, multinational trial sponsored by Eli Lilly and Company, which randomized more than 430 patients with malignant pleural mesothelioma to cisplatin with or without pemetrexed. That trial completed enrollment in February 2001 and is the largest trial ever conducted in mesothelioma. The second trial is being conducted by the European Organization for the Research and Treatment of Cancer (EORTC) and compares cisplatin with or without raltitrexed with planned accrual of 240 patients. In both trials, survival is the main endpoint. These trials will help to define the role of these new antifolates in malignant pleural mesothelioma.     

Low molecular weight heparin (LMWH) increases the efficacy of cisplatinum plus gemcitabine combination in advanced pancreatic cancer

BACKGROUND: In this non-randomized study we aimed to assess the efficacy of the addition of low molecular weight heparin (LMWH) to gemcitabine (GEM) plus cisplatinum (CDDP) combination chemotherapy on survival by prevention of thromboembolic complications in patients with advanced pancreatic cancer (APC). PATIENTS AND METHODS: Between November 1999 and February 2004, 69 consecutive patients with APC were treated with GEM (800 mg/m2, day 1, day 8) plus CDDP (35 mg/m2, day 1, day 8) every 21 days +/-LMWH (nadroparine calcium, 2,850 IU/day until disease progression). Ten out of 35 patients in LMWH group and 10 out of 34 patients in chemotherapy alone group had primary inoperable locally advanced disease and the rest of the patients had metastatic disease. RESULTS: Total response rate was 58.8% (11.7% CR) for the patients treated with LMWH and 12.1% for those treated without LMWH (P = 0.0001). LMWH group had a better median time to progression (TTP) and survival when compared to control group (7.3 vs. 4.0 months, P = 0.0001; 13.0 vs. 5.5 months, P = 0.0001). The toxicity was similar and acceptable in both groups. CONCLUSION: Addition of LMWH to GEM plus CDDP combination significantly improved the response and survival in patients with APC and the current schedule deserves to be tested in phase III trials.     

Treatments of pancreatic cancer from the standpoint of medical oncology

The early diagnosis of pancreatic cancer is difficult because of the lack of specific early symptoms,and surgery with curative intent can be performed in only 20% of patients. Chemotherapy for unresectable pancreatic cancer has been advancing ever since gemcitabine (GEM) was confirmed to provide a survival advantage in patients with advanced pancreatic cancer. For more than 20 years, the standard treatment for locally advanced diseases has been chemoradiotherapy using 5-FU, but more effective chemotherapy regimens are required. New standard treatments for locally advanced pancreatic cancer, including GEM chemotherapy and chemoradiotherapy using new agents, should be investigated. Several randomized clinical trials comparing GEM-based chemotherapy and GEM alone for the treatment of unresectable pancreatic cancer have been conducted, but a new standard chemotherapy regimen superior to GEM alone has not established. In Japan, phase II studies of S-1 or a combination of GEM and S-1 have produced promising survival rates, and a large phase III study using GEM and S-1 is necessary to establish the standard chemotherapy. Furthermore, second-line chemotherapy regimens for use after GEM chemotherapy should be investigated to improve the survival of patients with advanced pancreatic cancer.     

Tsunami of immunotherapy reaches mesothelioma

Malignant pleural mesothelioma (MPM) is the most common type of malignant mesothelioma. It is a rare tumor linked to asbestos exposure and is associated with a poor prognosis. Until very recently, patients with advanced or unresectable disease had limited treatment options, primarily based on doublet chemotherapy with cisplatin and pemetrexed. In 2020 and 2021, after more than a decade with no major advances or new drugs, two phase III clinical trials published results positioning immunotherapy as a promising option for the first- and second-line treatment of MPM. Immunotherapy has revolutionized the treatment of many cancers and is also showing encouraging results in malignant mesothelioma. Both immune checkpoint inhibition and dual cytotoxic T-lymphocyte–associated antigen 4 and programmed death-ligand 1 pathway blockade resulted in significantly improved overall survival in randomized phase III trials. In the CheckMate 743 trial, first-line therapy with nivolumab plus ipilimumab outperformed standard chemotherapy, while in the CONFIRM trial, nivolumab outperformed placebo in patients previously treated with chemotherapy. These two trials represent a major milestone in the treatment of MPM and are set to position immunotherapy as a viable alternative for treatment-naïve patients and patients with progressive disease after chemotherapy.     

The role of gemcitabine in the treatment of malignant mesothelioma

Gemcitabine is broadly active in a variety of solid tumors, including malignant mesothelioma. In vitro, gemcitabine demonstrates activity against mesothelioma cell lines. The role of single-agent gemcitabine in patients with mesothelioma is unclear, since three phase II trials treated a total of 60 patients and achieved response rates of 0%, 7%, and 31%. The combination of gemcitabine and cisplatin is synergistic against mesothelioma cell lines in vitro. Gemcitabine in combination with cisplatin or carboplatin shows definite activity in phase II trials. The trial by Byrne and colleagues that demonstrated a response rate of 48% established the combination of gemcitabine plus cisplatin as a standard therapy for this disease in the United States. Subsequent multicenter trials have achieved lower response rates of 26% and 16% for this combination. Gemcitabine plus carboplatin also has activity. Future roles for gemcitabine in malignant mesothelioma patients include incorporating a gemcitabine/platinum regimen for neoadjuvant or adjuvant therapy, combining it with other cytotoxic chemotherapy agents such as pemetrexed or vinorelbine, or adding novel cytostatic agents such as the vascular endothelial growth factor (VEGF) inhibitor, bevacizumab, to the gemcitabine and platinating agent combination.     

Efficacy of the combination of cisplatin with either gemcitabine and vinorelbine or gemcitabine and paclitaxel in the treatment of locally advanced or metastatic non-small-cell lung cancer: a phase III randomised trial of the Southern Italy Cooperative Oncology Group (SICOG 0101).

BACKGROUND: Triplet regimens were occasionally reported to produce a higher response rate (RR) than doublets in locally advanced or metastatic non-small-cell lung cancer (NSCLC). This trial was conducted to assess (i) whether the addition of cisplatin (CDDP) to either gemcitabine (GEM) and vinorelbine (VNR) or GEM and paclitaxel (PTX) significantly prolongs overall survival (OS) and (ii) to compare the toxicity of PTX-containing and VNR-containing combinations. PATIENTS AND METHODS: Stage III or IV NSCLC patients were randomly assigned to (i) GEM 1000 mg/m(2) and VNR 25 mg/m(2) on days 1 and 8 (GV arm); (ii) GEM 1000 mg/m(2) and PTX 125 mg/m(2) on days 1 and 8 (GT arm); (iii) GV plus CDDP 50 mg/m(2) on days 1 and 8 (PGV arm); and (iv) GT plus CDDP 50 mg/m(2) on days 1 and 8 (PGT arm). Treatments were repeated every 3 weeks for a maximum of six cycles. RESULTS: A total of 433 (stage III, 160; stage IV, 273) patients were randomly allocated to the study. RR was 48% [95% confidence interval (CI), 42% to 54%] for triplets and 35% (95% CI, 32% to 38%) for doublets (P = 0.004). Median progression-free survival (6.1 versus 5.5 months, P = 0.706) and median OS (10.7 versus 10.5 months, P = 0.379) were similar. CDDP significantly increased the occurrence of severe neutropenia (35% versus 13%), thrombocytopenia (14% versus 4%), anaemia (9% versus 3%), vomiting (6% versus 0.5%), and diarrhoea (6% versus 2%). Conversely, frequency of severe neutropenia (30% versus 17%) and thrombocytopenia (11% versus 6%) was significantly higher with VNR-containing regimens. CONCLUSIONS: Adding CDDP to GV or GT significantly increased RR, but did not prolong the OS of patients. Among doublets, the GT regimen should be preferred in view of its better safety profile.     

Systemic chemotherapy in the management of malignant peritoneal mesothelioma.

AIM: To review available evidence on the efficacy of chemotherapy in malignant mesothelioma of any origin. METHODS: All original research and review papers related to the role of systemic chemotherapy in the treatment of malignant mesothelioma, published from 1966 through February 2005, were identified through a MEDLINE search of the literature using the following search terms: "mesothelioma", "peritoneal", "chemotherapy", "antifolates", "cancer therapy". This search was supplemented by a manual search of the Proceedings of the Annual Meetings of the American Association for Cancer Research, American Society of Clinical Oncology, and the American Association for Cancer Research (AACR)-European Organization for Research and Treatment of Cancer (EORTC)-National Cancer Institute (NCI) Symposium on New Anticancer Drugs. RESULTS: Pemetrexed in combination with cisplatin is the first treatment regimen that demonstrates a survival improvement in patients with unresectable malignant pleural mesothelioma. Data from uncontrolled studies suggest similar antineoplastic efficacy in patients with mesothelioma of peritoneal origin. Preliminary results also suggest a possible survival advantage for a combination of cisplatin and raltitrexed as compared to cisplatin alone. Other cytotoxic agents that have shown to be active in this setting include vinorelbine and gemcitabine, either alone or combined with platinum compounds. CONCLUSION: The pemetrexed-cisplatin combination has become the new standard of care for patients with unresectable malignant mesothelioma. Future strategies shall incorporate these novel agents into multimodality approaches at earlier stages of the disease. Given the low incidence of this disease, encouraging physicians to refer these patients to specialized centers and patients to participate in clinical trials is of utmost importance.     

Refractory non-small-cell lung cancer responding to combination chemotherapy with docetaxel, gemcitabine and cisplatin

The combination of docetaxel (TXT), gemcitabine (GEM), and cisplatin (CDDP) produced a regression in a squamous cell carcinoma of the lung that had recurred after radiation therapy plus chemotherapy, and was resistant to the combination of carboplatin (CBDCA) with etoposide (ETP) or paclitaxel (TXL). The patient was a 62-year-old man with squamous cell lung cancer, which was first successfully treated by a combination of radiation therapy and chemotherapy, but showed local recurrence after 8 months. Although the recurrence was treated with CBDCA plus ETP and then TXL, the tumor continued to grow with symptomatic progression of airway stenosis. The tumor began to regress after the regimen of TXT, GEM and CDDP was started. This therapy achieved PR with symptomatic improvement. The combination of TXT, GEM and CDDP may be effective for recurrent non-small-cell lung carcinoma, even in patients that have failed to respond to more than one chemotherapy regimen.     

Clinical development of S-1 (TS-1) for advanced gastric cancer

The 5-FU plus cisplatin containing regimen like FP, ECF and DCF, is considered to be the most effective treatment for advanced gastric cancer in the United States, Europe, and Korea. In Japan, oral fluoropyrimidine S-1 (TS-1) is currently considered to be the first candidate as the standard drug for advanced gastric cancer. S-1 based combination therapies with other promising drugs like cisplatin, irinotecan and taxanes, are expected to yield good results. Above all, S-1+CDDP therapy showed a high efficacy and expected to be a standard therapy for advanced gastric cancer. Two large phase III studies, JCOG 9912 5-FU vs S-1 vs CPT-11 +CDDP and S-1 vs S-1+CDDP, are now on going to establish an acceptable frontline standard for patients with AGC. We therefore need to develop new agents and combination chemotherapy regimens to achieve a greater survival benefit in AGC.     

Weekly gemcitabine and cisplatin chemotherapy: a well-tolerated but ineffective chemotherapeutic regimen in advanced pancreatic cancer patients. A report from the Italian Group for the Study of Digestive Tract Cancer (GISCAD).

BACKGROUND: This phase II study was initiated to determine the activity and toxicity of a combination of gemcitabine (GEM) and cisplatin (CDDP) in patients with pancreatic cancer. PATIENTS AND METHODS: CDDP 35 mg/m(2) was given as a 30-min infusion and GEM 1000 mg/m(2) as a 30-min infusion. Both drugs were administered once weekly for 2 consecutive weeks out of every 3 weeks to chemonaive patients with locally advanced or metastatic pancreatic cancer. RESULTS: Forty-five advanced pancreatic cancer patients received this regimen for a total of 180 cycles of chemotherapy. One complete and four partial responses have been observed for an overall response rate of 9% (95% confidence interval 10% to 11%). Twenty-one patients (46%) had stable disease and 19 progressed on therapy. The median time to progression was 3.6 months, with a median survival of 5.6 months. A clinical benefit was obtained in nine of 37 patients (24%). Side-effects were mainly represented by hematological toxicity. Grade 3/4 WHO toxicities included neutropenia (6% of the patients) and thrombocytopenia (11%). The dose of GEM and CDDP was reduced in 14 patients (31%) and treatment was delayed in 10 patients (22%). CONCLUSIONS: Our results in terms of response rate, clinical benefit and survival do not support an advantage for the combination of GEM and CDDP given by this schedule.     

Combination chemotherapy with S-1 and carboplatin for head and neck cancers

Chemotherapy plays an important role in the treatment of head and neck cancer (HNC) patients with recurrent and/or metastatic unresectable disease. The standard regimen for HNC has been a combination of cisplatin (CDDP) and 5-fluorouracil (5-FU). We planned to develop a new outpatient regimen that could be carried out safely and had an antitumor activity equivalent to the regimen of CDDP plus 5-FU. For this purpose, we selected a combination of S-1 and carboplatin. The overall response rate of 40.9% in this study was almost equivalent to the study previously reported on 5-FU plus CDDP. This regimen of S-1 plus carboplatin has the possibility of yielding tumor responses equivalent to a conventional regimen of 5-FU combined with CDDP in patients with recurrent and/or metastatic head and neck carcinoma as a second-line palliative chemotherapy.     

Combination of low-dose cisplatin and gemcitabine for treatment of elderly patients with advanced non-small-cell lung cancer

PURPOSE: To evaluate the feasibility, toxicity and efficacy of the combination of low-dose cisplatin (CDDP) and gemcitabine (GEM) in elderly patients with advanced non-small-cell lung cancer (NSCLC). PATIENTS AND METHODS: This phase II trial included 46 patients aged 70 years or older with previously untreated advanced NSCLC. All patients were evaluable for response and toxicity. Treatment consisted of CDDP 50 mg/m(2) on day 1 plus GEM 1000 mg/m(2) on days 1 and 8. The regimen was repeated every 21 days. Patients received a minimum of three courses unless progressive disease was detected. RESULTS: A total of 190 GEM-CDDP courses were administered (median 4.1 courses per patient). The chemotherapy regimen was well tolerated. No patients developed grade 4 toxicity. Grade 3 toxicities were as follows: neutropenia in six patients (13%), and anemia, thrombopenia and nausea/vomiting in one (2%) each. Two patients (4%) had mild nephrotoxicity. Of the 46 patients, 16 had a partial response (35%, 95% confidence interval, CI, 28-52%), 17 (37%) remained stable and 13 (28%) had disease progression. Eastern Cooperative Oncology Group performance status improved in 17 patients (37%), whereas 25 (54%, 95% CI 44-74%) showed a clinical benefit. Median time to progression was 20 weeks. Overall median survival was 44 weeks, with a 1-year actuarial survival rate of 35%. CONCLUSIONS: The combination of low-dose CDDP and GEM for elderly patients with advanced NSCLC is an effective and well-tolerated chemotherapeutic approach.