[in Japanese]

View full abstract

Objective. To assess the important points of view from reading for chest CT images.Materials and Methods. CT images were examined due to the bronchial branching style and the density of abnormal areas. Results. It is important to understand the relation the lesions and pulmonary arteries, veins, and the secondary pulmonary lobules.Conclusion. Differential diagnosis should be done based on the lung inheritent structure including the secondary pulmonary lobules before the recognition of the abnormal shadows and density of lesions.

View full abstract

Oncologists for lung cancer should have good communication with a pathologist and understand caveats and information associated with pathology.This article gives an explanation about order form, how to handle cytological, biopsy or surgical materials, format of a pathological report of lung cancer, how to use a pathological consultation system, and so on.

View full abstract

The concept of bronchoscopic diagnosis is divided into endoscopic diagnosis which is obtained by observing lesions endoscopically and examinations to obtain cytologic and histologic specimens for definitive diagnosis. The latter is further divided into biopsy under direct endoscopic visual guidance and that under fluoroscopic guidance, similar to catheter examinations.
Lung cancers are divided into early and advanced lung cancers by the endoscopic diagnostic criteria of the General Rules for Clinical and Pathological Record of Lung Cancer, and the former is further classified into the mucosal thickening type, nodular type, and polypoid type. The advanced lung cancers are classified into intra-mucosal, sub-mucosal, and extra-wall types. The intra-mucosal type is divided into the mucosal thickening, nodular, and polypoid types.
Each histologic subtypes of lung cancer has its own characteristics bronchoscopically, however definitive diagnostic criteria have not yet been established. It is important to understand these characteristics of lung cancer to define the extent of cancer invasion and select the biopsy site of a lesion and biopsy methods, in addition to distinguishing between malignant and benign lesions.
The significance of bronchoscopy is easily ignored, because central type lung cancers are fewer and very small peripheral lung cancers which can be shown only by CT are increased in number at present. However, the minimally invasive nature of transbronchial approaches, which is one of the reasons to make bronchoscopy a standard examination for lung diseases, is also important for both diagnosis and treatment of these small lung cancers, and treatment of lesions located in the central airway, such as stent placement. Bronchoscopy will continue to be an important examination for conditions affecting the respiratory organs.

View full abstract

Basic theory and clinical application for lung cancer of FDG-PET, which recently attract attention, is described. PET has original features different from morphological diagostic modalities, such as CT or MRI. For various objects including staging, diagosis of recurrence, monitoring therapeutic effect, screening etc., PET may be effective and probable to add information to conventional imaging modalities. As PET has some defects, examination should be performed with entire understanding for the character of FDG-PET.

View full abstract

Since publication of the Radiologic Diagnostic Oncology Group Report (RDOG) in 1991, the clinical application of pulmonary magnetic resonance (MR) imaging to patients with lung cancer has been limited. CT has been much more widely available for staging of lung cancer in clinical situations. Currently, ventilation and perfusion scintigraphy is the only modality that demonstrates pulmonary function while FDG-PET is the only modality that reveals biological glucose metabolism of lung cancer. However, recent advancements in MR imaging have made it possible to evaluate morphological and functional information in lung cancer patients more accurately and quantitatively. Pulmonary MR imaging may hold significant potential to substitute for nuclear medicine examinations. In this review, we describe recent advances in magnetic resonance (MR) imaging of lung cancer, focusing on (1) characterization of solitary pulmonary nodules;(2) differentiation from secondary change; evaluation of (3) mediastinal invasion, (4) chest wall invasion, (5) lymph node metastasis, and (6) distant metastasis; and (7) pulmonary functional imaging. We believe that further basic studies, as well as clinical applications of newer MR techniques, will play an important role in the management of patients with lung cancer.

View full abstract

During the 1990's many irinotecan monotherapy trials for lung cancer were conducted. Irinotecan monotherapy against previously untreated advanced non-small cell lung cancer showed an overall response rate of 24.5% and median survival time of 6.2 to 10.8 months in 265 patients. There were grade 3 or 4 toxicity of leukopenia (25%), neutropenia (29%), diarrhea (21%), nausea/vomiting (22%) in the treatments. Diarrhea was an especially serious problem. In small cell lung cancer, most patients had been previously treated, yet in this group the overall response rate was 17.6%, with a median survival time of 4.6 to 6.1 months in 118 patients. Clinical trails in previously treated patients with non-small cell and small cell lung cancer are warranted. (JJLC. 2003;43: 832-836)

View full abstract

Objective and Methods. No cross-resistance is observed between irinotecan (CPT-11) and Carboplatin (CBDCA) in vitro. The two drugs show clinically different toxicity profiles and synergistic antitumor effect in cancer cells in vitro. Here, we describe the results of combination chemotherapy with CPT-11 and CBDCA, and a threedrug regimen including taxane, in lung cancer.Results. Phase I and II trials of CPT-11 and CBDCA yielded response rates of 79 to 89% in small-cell lung cancer, and in advanced non-small-cell lung cancer the response rules were 22 to 36% with a 1-year survival rate of 37.6 to 42.2%. CPT-11 and CBDCA including taxane yielded response rate of 32 to 56% and median survival time of 11 to 16 months in non-small-cell lung cancer, however, adverse events occurred more frequently than in CPT-11 and CBDCA. The principal toxicites of CPT-11 and CBDCA were leukopenia, neutropenia, thrombocytopenia, and diarrhea.Conclusions. CPT-11 and CBDCA have shown similar effectiveness to those of other chemotherapy regimens in lung cancer. This regimen is recommended especially for patients who cannot have cisplatin and have decreased cardiac or renal function, and is useful for chemotherapy of outpatients.

View full abstract

Irinotecan hydrochloride is highly active in the treatment of small-cell lung cancer (SCLC) both in single use and combination with cisplatin. The arm of irinotecan plus cisplatin (IP) every 4 weeks for 4 cycles has significantly better survival for extensive-disease SCLC compared with the arm of etoposide and cisplatin (EP) every 3 weeks for 4 cycles, which was very representative and fine between previously reported results, without any difference of treatment compliance in either arm. Significantly more myelosuppression was observed in the IP arm, but on the contrary, significantly severe diarrhea was observed in the IP arm, especially in the initial courses of the regimen. In the arm, approximately one third of patients skipped the administration of irinotecan on day 8 and/or day 15, which was subsequently related to less dose intensity. Even though, irinotecan plus cisplatin every four weeks is considered to be a new standard treatment regimen against extensive-disease SCLC with good PS. Another phase III study has been conducted to reconfirm the result. It may also be posible for tailor-made therapy including irinotecan administration by meaning UGT1A1 polymorphism, to avoid severe toxicities.

View full abstract

Two complete response (CR) cases were presented, treated by irinotecan chloride combination chemotherapy. One was 47-year old female with c T4N3M0 adenocarcinoma of lung. She was treated by 4 courses of cisplatin and irinotecan combination chemotherapy and became a CR. She has now a progression-free survival 2 years and a month after beginning of the treatment. Another case was 51-year old male with c T2N2M1 small cell carcinoma of lung. He was treated by 4 courses of cisplatin, irinotecan and etoposide combination chemotherapy and became a CR. He also has now a progression-free survival 3 years and 7 months after beginning of the treatment. CR rate of cisplatin and irinotecan combination chemotherapy against advanced non-small cell lung cancer is 1.6% and it has become around 10% of 2-year survival rate by platinum and new anticancer agent treatment. CR rate of irinotecan combination chemotherapy against extensive stage small cell lung cancer is now 10 to 20% and 2 and 3-year survival rate are around 20% and near 10%, respectively. There are only few cases of CR and long term survivors in patients with advanced lung cancer treated by chemotherapy. In near future, it is expected to better outcome of advanced lung cancer by introducing new agents including molecular targeted therapy.

View full abstract

Objective. To assess the efficacy of a new agent, Amrubicin (AMR), for non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC).Methods. We reviewed the results of phase I/II studies using AMR for advanced NSCLC, phase II studies using AMR for extensive disease (ED)-SCLC and phase I/II studies using AMR in combination with cisplatin for ED-SCLC.Results. Phase I/II studies for previously untreated advanced NSCLC were carried out using the dosing regimen of intravenous (iv) administration on 3 consecutive days as recommended by the pre-clinical studies. The dose-limiting toxicities were leukopenia, thrombocytopenia and gastrointestinal disturbance, the maximum tolerated dose was 50 mg/m2/day and the recommended dose for phase II studies was 45 mg/m2/day. Two phase II studies for advanced NSCLC were conducted and showed response rates of 27.9% and 18.3%, respectively. The phase II studies for ED-SCLC revealed a response rate of 75.8%(complete response rate 9.1%), and a median survival time of 11.7 months. The phase I/II study in combination with cisplatin showed the recommended dose was AMR 45 mg/m²/day and cisplatin 60 mg/m², the response rate was 88.6%(complete response rate 9.1%), and the one-year survival rate was 65.3%.Conclusion. These results are promising for the efficacy of AMR against NSCLC and SCLC. Further clinical trials will make clear whether AMR offers a significant benefit for practical medical treatment of lung cancer.

View full abstract

Vinorelbine monotherapyi s as effectivea nd clearlyl ess toxic than old cisplatin-basedd oublet in patients with advancedn on-small-celllu ngc ancer (NSCLC) C. omparedt o the best supportivec are, v inorelbinem onotherapy has been shown to improve survival and quality of life in elderly patients with advanced NSCLC. Therefore, this monotherapy is considered the treatment of choice for elderly or frail patients who cannot tolerate cisplatin-containing regimens. In addition, the combination of vinorelbine plus cisplatin may be superior to vinorelbine alone in NSCLC patients with a good performance status both in terms of response rate and survival duration

View full abstract

This paper reviews the clinical outcomes presently achieved for the combination regimen of vinorel -bine (VNR) plus cisplatin (CDDP) in advanced non-small-cell lung cancer (NSCLC). The combination regimen (VC) was more effective than VNR alone, CDDP alone, or CDDP plus old drugs. The results were almost identical to those obtained for combination regimens of platinum plus other new drugs. The main adverse reactions were neutropenia and nausea/vomiting.
Quality of life on VC was equivalent to that on platinum plus other new drugs. In terms of convenience, weekly VNR+CDDP (every 4 weeks) was inferior to paclitaxel+carboplatin (PCb) but appeared to be equivalent to VC every 3 weeks. The VC regimen is less expensive than PCb. There are problems with the dosing schedule of VNR in VC however, with VNR delivered on day 15 in less than 50% of patients receiving a regimen of VNR 25 mg/m²(weekly) and CDDP 80mg/m²(day 1) every 4 weeks. In contrast, analysis of data including that in our study revealed that the median delivered dose intensity was at least 90% for each course of CDDP and VNR (days 1 and 8) in a regimen of VNR 25mg/m²(days 1 and 8), CDDP 80 mg/m²(day 1) every 3 weeks, showing that VNR was administered almost in accordance with the schedule. The clinical outcome in a 3-weekly dosing schedule was a response rate of 29 to 57%, and mean survival was approximately 10 months. VC administered in a 3-weekly dosing schedule is therefore recommended.

View full abstract

Objective . To evaluate the efficacy and tolerability of combination chemotherapy with cisplatin (CDDP), vinorelbine (VNB), mitomycin (MMC), we performed a clinical study in patients with previously untreated advanced non-small cell lung cancer (NSCLC).Study Design. Patients with clinical stage-III or stage-IV and aged under 75 years old were entered in this study from 5 hospitals in the Saitama area. CDDP 80 mg/m²and MMC 8 mg/m²were administered intravenously on dayl. in inoperable case VNB 25 mg/m², and in pre-operative case VNB 20 mg/m²administered intravenously on dayl and 8. The treatment was performed every 4 weeks and we planned to perform 2 courses or more. Results. Forty six patients were enrolled with a mean age of 61 (range 39-72) years old, and 26 were clinical stage-IIIA, 10 were stage-IIIB and 10 were stage-IV.The mean number of performed courses was 1.6 (range 1-3 courses), and there were 2l cases with 2 or more courses.Toxicity of grade 3 or more consisted of 13 cases of leukocytopenia (28%), 6 cases of thrombocytpenia (13%), 4 cases of anemia (9%), 4 cases of nausea or anorexia (9%), 2 cases of phleb-itis (4%) and 1 case of acute renal failure (2%). There were no severe complications and no treatment-related death. The overall response rate was 37% with 13 partial response (PR), 18 no change (NC) and 4 progressive disease (PD) in 35 evaluable cases.Conclusion. The results indicate that the combination chemotherapy of CDDP, VNB, MMC has an anti-tumor activity in NSCLC that is comperarable to the standard combination chemotherapy of CDDP, vindesine (VDS), MMC, and it is well tolerated.

View full abstract

Objective. Surgicalt herapy remainst he treatment of choice for resectable non-small-cell ung cancer (NSCLC.) H oweverp, ostoperatives urvivali s far froma cceptable, except for patients with stage IA tumors.F urthermore, the efficacies of postoperative adjuvant therapies have not been well established. Under these circumstances, induction chemotherapyh as attracted widespreada ttentionf rom cliniciansa nd severalc omparativec linicals tudies on induction chemotherapy have reported favorable results. Therefore, the authors decided to conduct a pilot study to evaluate the efficacy and safety of triple induction chemotherapy for NSCLS using two new anti-cancer drugs, vinorelbine (VNR) and docetaxel (TXT), plus cisplatin (CDDP).Methods and Results. Thirty-three patients with unresectable NSCLC, who underwent triple chemotherapy and 25 patients with resectable NSCLC, who underwent induction chemotherapy (IC), were enrolled in this study. The overall NSCLC histological types consisted of 24 adenocarcinomas (Ad.), 28 squamous cell carcinomas (Sq.), and 6 large cell carcinomas (La.). The clinical stages of the patients were as follows: stage IIA, 3 patients; stage IIB, 8 patients; stage IIIA, 14 patients; stage IIIB, 18 patients; and stage IV, 15 patients. Among the IC cases, 9 patients had Ad., 13 patients had Sq., and 3 patients had La. The clinical stages of the patients who underwent IC were as follows: stage IIA, 3 patients; stage IIB, 7 patients; stage IIIA, 12 patients; and stage IIIB, 3 patients. The IC regimen consisted of VNR (25 mg/m²) administered on day 1, and TXT (60 mg/m²) administered on day 2; to ameliorate the adverse effects of these drugs, a total of 80 mg/m²of CDDP was administered for 5 consecutive days beginning on day 2 (25 mg/day for first 4 days and the remainder on day 6). The overall response rate was 46.6%(4 complete responses and 23 partial responses), and the number of chemotherapy courses was 104 (1.8 courses per person, on average). In 14 of the 25 IC subjects, down-staging was observed; 20 cases subsequently received curative resections. The resected primary lesions and dissected lymph nodes were histologically evaluated to evaluate the efficacy of the treatment. Based on this evaluation, the histopathological effects of Ef.3 and Ef.2 were reported to be 10% and 40%, respectively. However, in 4 out of 12 cases, where metastasis to the lymph nodes decreased after chemotherapy, residual cancer was histologically observed in the lymph nodes. The median survival time for the 33 patients with unresectable NSCLC was 6.4 months. The 1-year and 2-year survival rates were 31.2% and 13.4% respectively. Among the 25 patients who underwent IC, the 1-year and 2-year survival rates were 95.2% and 67.9%, respectively. The main adverse reaction related to hematological toxicity among these subjects was leukocytopenia. Grade 3/4 leukocytopenia was observed in 93.0% of the patients, but was ameliorated by granulocyte colony-stimulating factor (G-CSF) treatment. Other nonhematological toxicity-related adverse effects were nausea and vomiting. Grade 3 nausea and vomiting was observed in 28.1% and 24.6% of the patients, respectively. These adverse reactions were ameliorated by the administration of antivomiting agents (5-HT₃, metoclopramide) and liquid perfusions. No significant nephrotoxicity was observed.Conclusion. Triple chemotherapy using VNR, TXT, and CDDP was tolerated by subjects witha good performance status who were under the age of 70 years; this therapy might be effective for preoperative induction chemotherapy

View full abstract

Objective. We evaluated the efficacy and toxicities of nedaplatin plus vinorelbine treatment and nedaplatin plus gemcitabine treatment in non small cell lung cancer patients. Methods. VQ-nedaplatin 80mg/m² (day1) +vinorelbine 25mg/m² (day 1, 8) on every 3 weeks. GQ-nedaplatin 80mg/m² (day 8) + gemcitabine 1000mg/m² (day 1, 8) on every 3 weeks. Results. The response rate was 35.5% or higher, especially in squamous cell carcinoma in VQ treatment. There were no serious side effects in VQ treatment. The response rate was 42.8% and there were no serious side effects in GQ treatment. These result were no different compared with Cisplatin-based treatment. Conclusion. Nedaplatin may be useful as cisplatin and has no serious side effects, but it further evaluation will be necessary.

View full abstract

Objective. To evaluate the efficacy and safety of the nedaplatin (CDGP)-docetaxel (TXT) combination in patients with squamous cell lung cancer. Patients and methods. Thirty-two patients with histologically confirmed squamous cell lung cancer were treated and evaluated (2 with stage IIB, 11 with stage IIIA, 7 with stage IIIB, 9 with stage IV and 3 recurrent cases). There were 30 males and 2 females and their mean age was 65.3 (42-89). Five patients received previous chemotherapy and 10 received concurrent or sequential radiotherapy. Patients received CDGP (80-140mg/body) and TXT (80-140mg/body) on day 1 with 1, 000ml hydration. Treatment was repeated every four weeks. Results. Fifty eight courses were performed for 32 patients. The mean dosage per course of CDGP and TXT were 66.1mg/m² (49.1-82.4) and 65.8mg/m² (49.1-82.4) respectively. Two complete and 17 partial responses were observed (overall response rate (OR): 59.4%). The OR was 57.7% and 40.0% in patients without radiotherapy and with previous chemotherapy respectively. Thirteen patients were dead and 19 were alive at 10.7 months mean follow up time. The 1, 2 and three-year survival rate were 67.2%, 28.5%, 28.5% for all 32 cases and 62.6%, 11.9%, 11.9% in chemotherapy alone cases. Grade 3/4 leucocytopenia and thrombocytopenia occurred in 39 courses and 2 courses respectively. Grade 3/4 nausea/vomiting was observed in only one patient and there was no grade 3 nephrotoxicity. There was no treatment-related death. Conclusions. The nedaplatin-docetaxel combination is an active and safe regimen in squamous cell lung cancers.

View full abstract

Objective. To clarify the role of gemcitabine as a single agent inthe treatment of patients with advanced non-small cell lung cancer (NSCLC). Study Design. The results of the trials evaluating gemcitabine monotherapy for advanced NSCLC were reviewed. Results. Phase II studies of gemcitabine have shown consistent activity against NSCLC. The response rate was 20%, and the median survival was 40 weeks, which were similar to those obtained with other newer chemotherapeutic agents. Although the survival advantage of gemcitabine was not significant in a randomized trial comparing gemcitabine to best supportive care, gemcitabine as a single agent is as effective and less toxic than older cisplatin- based combinations. A recent randomized trial has compared gemcitabine as a single agent with a two-drug combination of gemcitabine and carboplatin. In this trial, the combination produced a significantly higher response rate and a superior survival compared with gemcitabinealone. Conclusion. Gemcitabine monotherapy is not the standard chemotherapy for advanced NSCLC patients with good performance status (PS). However it can be one of the treatment choices for elderly or poor PS patients, for whomthe safety of chemotherapy is particularly important.

View full abstract

Purpose. To evaluate the role of non-platinum, gemcitabine-based combination chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC). Method. Clinical trials of gemcitabine plus vinorelbine and gemcitabine plus docetaxel which were published in peer-review journals were reviewed in terms of efficacy and toxicity. Results. A phase III trial comparing gemcitabine plus vinorelbine with cisplatin -based regimens demonstrated a non-significant slight survival disadvantage with gemcitabine plus vinorelbine. Global QoL is not improved with gemcitabine plus vinorelbine, although it is less toxic than cisplatin-based regimens.A randomized trial comparing docetaxel plus gemcitabine with cispaltin plus docetaxel demonstrated similar response rate, time to tumor progression, overall survival, and two-year survival rate. Conclusion. Gemcitabine-based two drug combination is active in patients with advanced NSCLC with less gastrointestinal toxicity than standard cisplatin-based chemotherapy. Non-platinum gemcitabine-based chemotherapy could be a treatment option in patients with advanced NSCLC.

View full abstract

et combination chemotherapy consisting of cisplatin (40 mg/m²), vinorelbine (20 mg/m²) and gemcitabine (800 mg/m²) which was administered days 1 and 8, every 4 weeks, was performed in patients with advanced non-small cell lung cancer in the National Kyushu Cancer Center and a multi-institutional phase II trial.During about 2 years from May 2000, 57 patients received the chemotherapy in Kyushu Cancer Center. Those patients had the following characteristics: mean age of 58 years (37-76 years); male/female, 34/23 patients; 54 with ECOG PS 0, 1; 51 with adenocarcinoma; stage IIIB/IV, 9/48; presence/absence of prior chemotherapy, 33/24.The main adverse event was hematologic toxicity. Grade 3/4 neutropenia and thrombocytopenia was observed in 33/40% and 18/0% of the patients. The grade 3 non-hematologic adverse event was observed only in two patients who had febrile neutropenia. Among 54 patients with assessable lession, 3 and 24 patients achieved CR and PR, respectively. As a result, the overall response rate was 50% in the total 54 patients and 66% in 24 patients without prior chemotherapy. Median survival time of all 57 patients was 14.4 months. A multi-institutional phase II trial using this combination chemotherapy in patients without prior chemotherapy started from April 2002 and the interim analysis was performed in 28 patients. Nineteen (68%) patients achived PR. The main adverse event was hematologic toxicity which was expected and manageable. A total of 115 cycles was administered and 21 patients (75%) could receive more than 4 cycles. We continue this phase II trial.

View full abstract

[in Japanese]

View full abstract

Objective. To confirm the safety and effectiveness of combination therapy with carboplatin plus taxol in Japanese patients with non-small cell lung cancer (NSCLC). Methods. For inoperable patients with stage III NSCLC, concurrent chemoradiotherapy with carboplatin plus taxol was done. Forty-five mg/m² of taxol plus AUC=2 dose of carboplatin were given weekly and radiotherapy was done concurrently at a dose of 1.8-2.0 Gy/day (total dose of 60-65 Gy). When CR or PR was obtained, weekly chemotherapy was added upto 16 weeks. On the other hand, previous phase I trial have shown that the recommended doses in biweekly administration of carboplatin and taxol were AUC = 3 (carboplatin) and 140 mg/m² (Taxol), respectively. Based on the result, we have conducted a phase II trial. Result. For chemoradiotherapy, 72 patients were registered and 68 patients were eligible. In 61 evaluable patients, CR was obtained in 4 patients, PR was in 40 patients, and the response rate was 72%. In interium analysis, estimated median survival time was 14 months and one-year survival rate was 56%. There were 3 cases with treatment related death; interstitial pneumonia, pneumocystis carinii pneumonia which occurred after the recovery from bone marrow suppression, and mediastinitis due to radiation necrosis. For protocol in advanced NSCLC, registration of all 80 patients has finished. So far, interium analysis has finished in 23/80 patients;≥grade 3 leukopenia was seen in 21% patients, ≥grade 3 neutropenia in 46%, fever in 3%, allergy in 3%, and fatigue in 3%, respectively. Eight of 21 patients evaluated was judged to be PR, and response ratio was 38%. Conclusion. Although they are interium analysis, the combination of carboplatin and taxol appeared safe and effective in Japanese patients.

View full abstract

Objective. The final report of a specialist committee on interstitial lung disease (ILD) induced by gefitinib in Japan was reviewed.Methods. One hundred and fifty-two cases, diagnosed with ILD induced by gefitinib, were evaluated on clinical characteristics, risk factors in fatality after onset of ILD, computed tomography (CT) findings and pathological findings in autopsy cases.Results. It was presumed that an incident and a mortality rates were 1.9% and 0.6%, respectively. Both rates revealed six-fold value compared with that in foreign countries. Although ILD frequently occurred within four weeks after administration during initial phases, onset of ILD tended to get later since then. Clinical features of early-onset cases were characterized by rapid progression and high mortality rate. Risk factors in fatality after onset of ILD were gender (male), histological type (squamous cell carcinoma), preexistence of idiopathic pulmonary fibrosis (IPF) or other interstitial pneumonias (IP) and performance status (≥2). Radiographic patterns of ILD on computed tomography (CT) were similar to those of ILD induced by other drugs. Pathological findings in autopsy cases basically showed diffuse alveolar damage (DAD). Conclusion. The most significant risk factor in fatality after onset of ILD was preexistence of IPF or other IP. So that gefitinib should be administered with caution in existence of them. In future, a prospective study is warranted to demonstrate an incident rate, risk factors and mechanisms of ILD.

View full abstract

Although a meta-analysis and a randomized study have shown that platinum-based chemotherapy yields a survival benefit in first-line treatment of advanced non-small-cell lung cancer (NSCLC), this benefit is only modest. Several new generation drugs (docetaxel, paclitaxel, vinorelbine, gemcitabine, and irinotecan) have demonstrated substantial antitumor activity in a first-line setting. Several phase II studies reconsidering the usefulness of second-line therapy were subsequently performed with each new agent. Among such agents, docetaxel yielded the most promising results, with response rates of 16-25%. One Japanese cooperative phase II study in the first-line setting (In Japan docetaxel has been used at a relatively lower dose in both clinical trials and clinical treatment than in European and American countries.) a response rate slightly lower (18.7%) than, but not significantly different from, other phase II trials at higher doses. The median survival time (42 weeks) and the severity of neutropenia, dose-limiting tyoxicity of docetaxel, were comparable to those in earlier European and American phase II trials. These results suggested that it was reasonable to assess the efficacy and toxicity of low-dose docetaxel (60 mg/m²) for previously treated advanced NSCLC. Thus we consider treatment by docetaxel for advanced NSCLC.

View full abstract

Object. Docetaxel and carboplatin (DC) have demonstrated activity as radiation sensitizers in preclinical studies. The aim of this phase II study was to evaluate the efficacy and toxicity of DC with concurrent thoracic radiation therapy (TRT) followed by consolidation chemotherapy with DC for stage III unresectable non-small-cell lung cancer (NSCLC). Methods. Thirty-three previously untreated patients with inoperable, locally advanced NSCLC received docetaxel 30 mg/m² over 1 hour and carboplatin at an AUC of 3 every 2 weeks for six cycles-four cycles during concurrent chemoradiotherapy and two cycles following completion of radiotherapy. Concurrent TRT was performed in 2-Gy daily fractions to a total dose of 60 Gy. Results. Among 32 evaluable patients, the overall response rate was 91%, with two complete responses and 27 partial responses. Median survival time by intention-to-treat analysis was 27 months, with survival rates of 76% at 1 year and 61% at 2 years. Serious side effects were generally limited to grade 3 neutropenia in 6%, grades 3 and 4 pulmonary toxicity in 6% and 3%, respectively, and grade 3 esophagitis in 3% of patients. Conclusion. DC with concurrent TRT followed by consolidation chemotherapy was highly active with manageable toxicity in patients with stage III unresectable NSCLC.

View full abstract

Objective. to evaluate the efficacy and toxicity of nonplatinum sequential triplet combination chemotherapy for advanced non-small-cell lung cancer. Patients and Study Design. this is a multi-institutional phase II study in 44 chemotherapy-naive patients with advanced NSCLC were treated with gemcitabine 1000mg/m² and vinorelbine 25mg/m², iv, days 1, 8, q3 weeks for three cycles. Docetaxel 60mg/m² was then administed, i. v, day 1, q3 weeks for three cycles. Results. objective response rate was 47.7% by RECEST. Median survival time was 15.7 months and 1- year survival rate was 59%. In the GEM/VNR cycles, grade 3/4 neutropenia occurred in 36.3%, grade 3/4 anemia in 4.5% and grade 3 thrombocytopenia in 2.3%. Grade 3 pneumonitis occurred in two patients (4.5%). In the DOC cycles, grade 3/4 neutropenia occurred in 39.4%. 33 patients completed three cycles of GEM/VNR and 22 patients completed six cycles of planned chemotherapy. There was no treatment related death. Conclusion, this regimen was very active and well tolerated. This study forms the basis for an ongoing phase III trial of Japan-SWOG common arm trial that compares this regimen and standard doublet combination (carbopaltin/paclitaxel).

View full abstract

Objective. Generally speaking, it is difficult to cure recurrence after resected non-small cell lung cancer (NSCLC). Treatment options regarding second therapy have been limited so far because of poor prognosis. Recently, a number of new agents which have favorable efficacy and toxicity have been introduced. This report shows the clinical experiences of gemcitabine (GEM) and vinorelbine (VNR) combinations in recurrence after resected NSCLC. Patients and Methods. From March 2001 to October 2002, 19 patients with recurrence after resection of NSCLC received combination chemotherapy of GEM 800 mg/m² and VNR 20 mg/m² biweekly in the outpatient clinic. Results. The mean age was 68.2 years with 12 men and 7 women. The types of histology were adenocarcinoma (n=17) and adenosquamous (n=2). Metastatic sites included: lung (n=12), lymph nodes (n=10), malignant effusion (n=4), bone (n=3), skin (n=2), brain (n=2), liver (n=1). The mean number of prescriptions of combination chemotherapy per patient was 14.2. Gradel-2 myelosuppression (n=12), general fatigue (n=9), anorexia (n=4), stomatitis (n=1) and phlebitis (n=1) was seen. Objective responses were; complete response (CR): 2/19 (10.5%), partial response (PR): 6/19 (31.6%), no change (NC): 7/19 (36.8%), progressive disease (PD): 4/19 (21.1%). Quality of life (QOL) during treatment in all patients has been stable. Conclusion. The regimen of GEM and VNR combination chemotherapy in the outpatient clinic represents a tolerable and effective treatment to apply in the palliative treatment of relapsed NSCLC.

View full abstract

Background. We report a case of refractory non-small-cell lung cancer responding to combination chemotherapy with gemcitabine (GEM) and cisplatin (CDDP). Case. The patient was a 60-year-old women with adenocarcinoma of the lung. An effective radiation therapy was performed for the cervical lymph nodes metastases found 19 months after the operation. Right adrenal metastasis and abdominal paraaortic lymph nodes metastases were detected 11 months later, and chemotherapy with CDDP was administered. Although temporary partial response was obtained, the metastatic lesion was refractory to CDDP. The patient was treated with GEM and CDDP, which result in nearly complete response which continued for 3 months. Conclusion. The combination therapy of GEM and CDDP may be effective for recurrent non-small-cell lung cancer refractory to other regimens.

View full abstract

Purpose. In the has 4 years, we performed chemotherapy using paclitaxel (TXL) for 20 cases of recurrentnon-small cell lung cancer and two cases of residual lung cancer patients. In this report, we present two cases showing complete remission. Case 1. The patient was a 69-year-old man who underwent an operation for stage IA adenocarcinoma.Thirty-eight months after the operation, this patient showed intrathoracic recurrence. No response was available after three couses of treatment using CDDP+VDS. This case was diagnosed as metachronous double primary lung cancer after the re-operation. Multiple recurrent tumors appeared in his left lung. Complete response was obtained after four courses of CBDCA+TXL. The patient is alive with no recurrence after seven courses of weekly TXL. Case 2. A 50-year old women underwent a non-curative operation for the tumor in the right S10 with intrathoracic dissemination.The pathological diagnosis was pT4NOM1, stage IV. The weekly TXL therapy was started because the residual tumors revelaed no response to the three courses of CBDCA+TXL. Complete response was obtained 20 months after the weekly TXL, therapy was started. The patient is alive with no sign of recurrence after 25 courses of weekly TXL therapy. Conclusion. Chemotherapy using TXL may be a promising regimen for the treatment of recurrent or residual non-small cell lung cancer.

View full abstract

Background. Standard treatment for locally advanced non-small-cell lung cancer has not yet established. Case. The patient was 58-year-old man with locally advanced squamous cell carcinoma (cT4N2M0, stage IIIB). The tumor, which was directly invading subcarinal lymph nodes and the esophagus, was located in the subcarinal space. He was treated with three cycles of chemotherapy with cisplatin and docetaxel. The reduction rate of the tumor size was 59%. No findings of the invasion to the esophagus were recognized after chemotherapy, enabling it to be completely resected. The operation of bilobectomy of right middle and lower lobe with combined resection of the subcarinal lymph nodes and the muscle layer of esophagus was performed. The pathological examination revealed neither residual tumor cells in the resected specimen nor lymph node metastasis, only fibrosis.Conclusion. Preoperative chemotherapy with cisplatin and docetaxel might be effective in locally advanced non-small cell lung cancer patients.

View full abstract

Background. The recent introduction of the new agents improved response rates in non -small cell lung cancer, but only a few cases achieved complete response.We reported a case of recurrent pulmonary adenocarcinoma achieving complete response by combination chemotherapy of cisplatin (CDDP) and docetaxel (TXT).Case. A 60-year-old man suffered from pulmonary adenocarcinoma and underwent left upper lobectomy with mediasti -nallymph node dissection, and combined resection of the pericardium and the phrenic nerve on April 17, 1995.The tumor was located in left S3, 5 cm in size, and invaded to the pericardium and the phrenic nerve. The tumor consisted of a mixture of moderately differenciated adenocarcinoma and signet-ring adenocarcinoma (p-T4N2M0, stage IIlb). Adjuvant chemotherapy with CDDP, vindesine, mitomycin C was performed and radiotherapy of 60 Gy was added. Four years after the operation, the right paratracheal and supraclavicular lymph node metastases appeared. Two courses of chemotherapy with CDDP and TXT were administrated and complete response was obtained. Two years and three months later, left axillar lymph node metastasis appeared and another 2 courses of chemotherapy with CDDP and TXT were administrated. The patient is alive and well without any sign of recurrence, 4 years after the first chemotherapy with CDDP and TXT.
Conclusion. Combination chemotherapy of CDDP and TXT was effective against recurrent pulmonary adenocarcinoma.

View full abstract

The published studies about cost-benefit or cost-minimisation analysis of cisplatin plus vinorelbine (CV) versus carboplatin plus paclitaxel (PCb) for patients with advanced non-small-cell lung cancer are very limited.One f them is an eonomic analysis alongside Southwest Oncology Group Trial S 509 to estimate the costminimisationof CV versus PCb. The other is the Italian Lung Cancer project which compares gemcitabine + cisplatin (GC) vs vinorelbine + cisplatin (VC) vs PCb. The latter is from the abstract of ASCO 2003. These two studies are referredto. In the former study, treatment with carboplatin plus paclitaxel is substantially and statistically significantly more expensivethan treatment with cisplatin plus vinorelbine.The majority of the cost difference is due to the additional cost ofthe protocol chemotherapy (approximately $12, 000). In the latter study, total mean cost in euros was GC 7892, VC6849 and PCb 10013; cost per cycle in euroswas GC 1963, VC 2107 and PCb 2367 per patient. Although the cost of PCbis higher than VC, the reason why PCb is used more often than VC may be due to other factors such as toxicity and convenience.

View full abstract

[in Japanese]

View full abstract

Ojective. The effectiveness of sputum cytology screening for detection of lung cancer in Osaka Lung Project was studied. Methods. Participants who were 40 years of age or older and with a cigarette index of 400 or more were screened annually by both sputum cytology and chest X-ray for the early detection of lung cancer in 8 local communities in Osaka since 1981. Results. In the Osaka Lung Project, during the 20 year period from 1981-2000, 235 cases of lung cancer were detected among 297, 628 participants. Lung cancers were detected in 130 high-risk persons. Of the 130 cases, 64 cases were squamous cell carcinoma. Thirty-six of these 64 persons were central-type squamous cell carcinoma. Out of the 36 cases 34 were detected by sputum cytology. The detection rate of central-type squamous cell carcinoma by sputum cytology for recent 5 years since 1996 decreased to about a half of the previous 15 years. Conclusion. Sputum cytology is the most effective method for detection of central type early lung cancer in high-risk group. To improve the detection rate of lung cancer by sputum cytology, it is important to screen the high risk group of over 50 years old men and to control the quality of sputum cytology

View full abstract