膀胱癌电切术后膀胱灌注多柔比星脂质体治疗浅表性膀胱癌的疗效观察

目的:探讨经尿道电切术后膀胱灌注多柔比星脂质体治疗浅表性膀胱癌的临床疗效。方法:78例患者随机分为2组:表柔比星灌注组（EOX）和多柔比星脂质体组（DOL）,随访比较2组患者术后复发情况和不良反应。结果:术后12个月和24个月,DOL复发率分别为5.0%和10.0%,明显低于EOX复发率18.4%和26.3%（P<0.05)。DOL组不良反应发生率低于EOX组（P<0.05）。结论:经尿道膀胱肿瘤电切术后膀胱灌注多柔比星脂质体疗效优于表柔比星而不良反应发生率低于表柔比星。     

Intravesical instillation of doxorubicin or epirubicin for chemoprophylaxis of superficial bladder cancer--the fifth study of the Japanese Urological Cancer Research Group for Adriamycin/Farumorubicin

A total of 465 patients with primary and multiple or recurrent, stages Ta and T1 superficial bladder cancer were included in this randomized multicenter trial to compare the prophylactic effect by 17 times instillation of 40 mg doxorubicin or 40 mg epirubicin with no instillation after transurethral resection of tumor(s). The primary endpoint was first recurrence after transurethral resection. Endoscopic examination as well as urinary cytology was performed in each case every three months. It became evident that the recurrence rate in the doxorubicin or epirubicin instillation arm was lower that in the no instillation arm. Toxicity was mainly restricted to bladder irritation in about 10% of patients in each instillation arm.     

Prevention of Recurrence of Superficial Bladder Cancers: Intravesical Instillation of Bacillus Calmette-guerin versus Bacillus Calmette-guerin plus Epirubicin

Purpose The short-term effects of intravesical chemoimmunotherapy with epirubicin and Bacillus Calmette- ‍Guerin (BCG) administered repeatedlly for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were ‍investigated in 22 patients with a median of 70 years between March, 1995 and February, 1999, and were compared ‍with those of BCG monotherapy in 50 patients between March, 1995 and February, 1999. ‍Patients and Methods The patients underwent intravesical instillation of Tokyo-strain BCG with or without ‍epirubicin after transurethral resection (TUR) of bladder cancer. For the combined treatment, at 1❛2 weeks after ‍TUR, epirubicin (40 mg) and BCG (80 mg) were instilled into the bladder by turn once a week for 12 weeks. For the ‍BCG alone group, 80 mg instillation were performed with the same schedule. Thereafter, the patients were followed ‍by cystoscopy and urinary cytology every 3 months for up to 3 years after intravesical therapy. ‍Results and Conclusions The simple recurrence rate was 22.7% (5/21) in patients with chemoimmunotherapy ‍and 32.0% (16/50) in BCG-treated patients. Adverse reactions, including increased frequency of urination, urgency ‍and miction pain, were observed in 18 patients (85.7%) undergoing chemoimmunotherapy and 58.0% undergoing ‍BCG monotherapy. One patient receiving chemoimmunotherapy was withdrawn from treatment because of severe ‍bladder-irritation symptoms due to instillation. Intravesical chemoimmunotherapy using epirubicin and BCG was ‍inferior in comparison with BCG monotherapy for prophylaxis of recurrence of superficial bladder cancer.     

Randomized study of single instillation of epirubicin for superficial bladder carcinoma: long-term clinical outcomes

PURPOSE: Intravesical instillation of epirubicin (EPI) is one of the most effective adjuvant therapies for nonmuscle-invasive bladder cancer postoperation. We evaluated the long-term efficacy of single dose intravesical epirubicin for superficial bladder carcinoma recurrence. METHODS: Between June 1997 and May 1998, a total of 47 patients with resectable superficial bladder carcinoma (Ta-1, Grade 1-2), primary or recurrent with no recurrence during last one year, were enrolled in this study. All patients were randomized into 3 study groups: Group A-single epirubicin (80 mg/40 mL of normal saline) was administered into the bladder within 6 hours postoperation; Group B-40 mg Epirubicin consecutively; Group C-40 mg mitomycin C, consecutively. In Group B and C, instillation were given every week for 6- 8 weeks and then every one month for 10 months. Patients were followed up at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months of treatment. The analyzed background factors were the therapeutic method, tumor recurrence, and side effects. RESULTS: Of the 47 patients, 43 (91.5 percent) were eligible and were followed up for 5 years postoperation. The disease free intervals of the three groups were found to have no significant differences (F = 10.28, p > 0.05). The recurrence rates were 35.7 percent (5/14), 33.3 percent (5/15), and 40 percent (6/15), respectively (chi(2)= 0.83, p > 0.05). Side effects of group A (13.6 percent) was lower than that of Group B or C (53.3 percent and 46.7 percent, respectively) significantly (chi(2) test, p < 0.01). CONCLUSIONS: These data indicate that single dose of epirubicin instillation postoperation can reduce the recurrence of superficial bladder carcinoma and has low side effects.     

上尿路移行细胞癌术后预防性膀胱灌注的临床研究

目的:探讨上尿路移行细胞癌术后预防性膀胱灌注的有效性。方法:61例上尿路移行细胞癌患者行根治性切除术,其中34例患者术后预防性使用吡柔比星膀胱灌注,27例患者单纯随访,比较两组患者2年内膀胱肿瘤的发生率以及发生时间,并观察药物灌注毒副反应发生的情况。结果:吡柔比星灌注组膀胱癌发生率为14.7%,观察随访组膀胱癌的发生率为37.0%,差异有统计学意义(P<0.05),再发时间分别为20个月和14个月,二者比较差异有统计学意义(P<0.05)。患者灌注过程中均耐受,未出现中止灌注的情况。结论:本研究初步显示,吡柔比星预防性膀胱灌注可有效减少膀胱肿瘤的发生,毒副反应少,值得临床推广。     

A comparative study of doxorubicin and epirubicin in patients with metastatic breast cancer

Seventy-seven patients with progressive metastatic breast cancer refractory to prior therapy participated in a prospective randomized trial designed to compare the efficacy and toxicity of doxorubicin and epirubicin administered as single agents. In arm 1, 60 mg/m2 of doxorubicin and, in arm 2, 90 mg/m2 of epirubicin were administered by 48-h continuous i.v. infusion every 3 weeks. In arm 3, 90 mg/m2 of epirubicin was administered by bolus every 3 weeks. Patients in the three groups had similar characteristics, except that in arm 3 more patients were premenopausal, had more extensive disease, and fewer patients had been exposed to doxorubicin. Objective remission rates were 29, 26, and 13%, respectively for the three arms. Median response durations ranged from 4-6 months. No significant differences occurred in response rate, remission duration, or survival among patients in the three arms. The incidence of gastrointestinal toxicity and alopecia was evenly distributed. Hematologic toxicity was more severe in arms 2 and 3, and there was a higher incidence of infectious complications in arms 2 and 3 compared to arm 1 (p = 0.05). Two episodes of congestive heart failure occurred in arm 1, one in arm 2, and three in arm 3. Although the total cumulative anthracycline dosage was highest in the arm 2 group, they had the lowest incidence of cardiac toxicity. Epirubicin by bolus and doxorubicin administered by continuous infusion have similar potential for cardiac toxicity. Epirubicin administered by continuous infusion appears less cardiotoxic than doxorubicin by either method of administration or epirubicin given by bolus. Epirubicin appears equally active and less cardiotoxic than the parent compound doxorubicin in patients with metastatic breast cancer.     

Phase II trial of weekly 4-epi-doxorubicin (epirubicin) in squamous cell carcinoma of the head and neck

We tested 4'-epi-doxorubicin (epirubicin) in 15 patients with advanced squamous cell carcinoma of the head and neck which progressed after conventional therapy. The drug was administered at the dosage of 25 mg/m2 weekly. No patient achieved objective response. Toxicity was minimal. Epirubicin given at this dose and schedule revealed no activity in heavily pretreated patients with cancer of the head and neck.     

不同剂量表柔比星膀胱灌注预防浅表性膀胱癌复发的疗效与安全性

目的比较不同剂量表柔比星膀胱灌注预防浅表性膀胱癌术后复发的疗效和安全性。方法90例浅表性膀胱癌患者根据开放的、前瞻性的、随机分组的方法,分别采用不同剂量表柔比星膀胱内灌注化疗,随访2年,观察患者肿瘤复发和不良反应。结果表柔比星80mg单次灌注组、40mg多次灌注组和50mg多次灌注组术后1年复发率分别为16．7％、13．3％和16．7％,2年复发率分别为50．0％、36．7％和36．7％。3组术后1年复发率差异无统计学意义（P〉0．05）,但2年时单次灌注组的复发率显著高于多次灌注组（P〈0．05）。表柔比星80,职单次灌注组、40mg多次灌注组和50mg;多次灌注组的不良反应发生率分别为23．3％、40．0％和33．3％,灌注次数愈多,不良反应发生率愈高。结论表柔比星术后早期、单次、大剂量灌注配合每月1次低剂量灌注预防浅表性膀胱癌复发,可能是一种安全、经济、有效的方法。     

Pharmacokinetics and metabolism of epirubicin administered as i.v. bolus and 48-h infusion in patients with advanced soft-tissue sarcoma.

We have studied the pharmacokinetics of epirubicin after its administration in sarcoma patients either as an i.v. bolus or as a 48-h infusion (5 courses each; 9 patients in total). Bolus injection was followed by a three exponential decay in plasma, with half-lives of 2.43 min, 1.95 h and 21.7 h; 48-h infusions were characterized by the very rapid establishment of a plasma plateau concentration followed by a biexponential decay after stopping the infusion. Pharmacokinetic parameters such as total plasma clearance, total volume of distribution, mean residence time and elimination half-life were similar, irrespective of the duration of the administration. In contrast, the relative amounts of the metabolites of epirubicin were reduced when the drug was administered over 48 h; in particular, the plasma levels of epirubicin glucuronide never exceeded those of epirubicin, which always occur after bolus injection. This may result from a lower availability of epirubicin for metabolism. These results now require validation in a larger group of patients using a cross-over design.     

NC‐6300, an epirubicin‐incorporating micelle,extends the antitumor effect and reduces the cardiotoxicity of epirubicin

Epirubicin is widely used to treat various human tumors. However, it is difficult to achieve a sufficient antitumor effect because of dosage limitation to prevent cardiotoxicity. We hypothesized that epirubicin‐incorporating micelle would reduce cardiotoxicity and improve the antitumor effect. NC‐6300 comprises epirubicin covalently bound to PEG polyaspartate block copolymer through an acid–labile hydrazone bond. The conjugate forms a micellar structure of 40–80 nm in diameter in an aqueous milieu. NC‐6300 (10, 15 mg/kg) and epirubicin (10 mg/kg) were given i.v. three times to mice bearing s.c. or liver xenograft of human hepatocellular carcinoma Hep3B cells. Cardiotoxicity was evaluated by echocardiography in C57BL/6 mice that were given NC‐6300 (10 mg/kg) or epirubicin (10 mg/kg) in nine doses over 12 weeks. NC‐6300 showed a significantly potent antitumor effect against Hep3B s.c. tumors compared with epirubicin. Moreover, NC‐6300 also produced a significantly longer survival rate than epirubicin against the liver orthotopic tumor of Hep3B. With respect to cardiotoxicity, epirubicin‐treated mice showed significant deteriorations in fractional shortening and ejection fraction. In contrast, cardiac functions of NC‐6300 treated mice were no less well maintained than in control mice. This study warrants a clinical evaluation of NC‐6300 in patients with hepatocellular carcinoma or other cancers.     

Epirubicin in the treatment of malignant mesothelioma: a phase II cooperative study. The North-Eastern Italian Oncology Group (GOCCNE)--Mesothelioma Committee

From September 1986 to April 1988, all consecutive patients with histologically proven (pathologic review mandatory) malignant mesothelioma, measurable disease, age less than 75 years, Karnofsky performance status equal to or greater than 40, and no previous chemotherapy were treated with epirubicin at the dosage of 75 mg/m2 i.v. every 3 weeks. Of the 23 patients who entered the study, 2 were retrospectively found not to have malignant mesothelioma. In the 21 eligible patients (all evaluable), no complete remission, 1 partial remission, 11 stable diseases and 9 progressions were noted. Toxicity was very mild. Median survival was 7.5 months. At the dosage used, epirubicin proved to be of little value in the management of these patients. Whether higher doses are more effective, as has been noted in other tumors, remains to be ascertained.     

Salvage treatment with epirubicin and/or paclitaxel in metastatic breast cancer patients relapsed after high-dose chemotherapy with peripheral blood progenitor cells

AIMS AND BACKGROUND: To evaluate feasibility and efficacy of paclitaxel as a single agent or in combination with epirubicin in breast cancer taxane-naive patients who have failed previous high-dose chemotherapy. METHODS: Since February 1995, we have treated 32 patients in first relapse or progression after high-dose chemotherapy. Nineteen patients had metastatic breast cancer, 12 more than 3 involved axillary lymph nodes, and 1 inflammatory breast cancer at inclusion to the program. The median time to relapse after high-dose chemotherapy was 12 months (range, 2-43). At relapse, 12 patients were treated with epirubicin (90 mg/m2) plus paclitaxel (175 mg/m2) administered on day 1 every 21 days. In 20 patients who had previously received more than 350 mg/m2 of a cumulative dose of epirubicin and in one patient pretreated with chemotherapy containing mitoxantrone, we employed paclitaxel (175 mg/m2) alone. A median number of five courses was administered (range, 2-10). RESULTS: The overall response rate after 3 courses (29 of 32 patients were assessable) was 55% and after 6 courses (21 of 32 patients were assessable) was 57%. The median time to progression was 7 months (95% CI, 5.7-9.2), and median survival was 27.5 months (95% CI, 17.8-37.0). Toxicity was recorded for 180 cycles (epirubicin + paclitaxel for 62 cycles and paclitaxel alone for 118 cycles). The main toxicity in both regimens was hematologic. We observed WHO grade 3-4 neutropenia (in 8 patients, 25%), for which G-CSF (5 microg/kg/day s.c.) was employed. WHO grade 3-4 thrombocytopenia occurred in 2 patients (6%) and WHO grade 3 anemia in 1 patient (3%). CONCLUSIONS: Our study showed that paclitaxel (alone or in combination with epirubicin) is feasible as salvage treatment in heavily pretreated patients.     

Improved anti-tumor activity of stabilized anthracycline polymeric micelle formulation, NC-6300

Anthracyclines have long been considered to be among the most active agents clinically available for the treatment of breast cancer despite their toxicity. To improve their pharmacological profiles, a new macromolecular prodrug, denoted NC-6300, was synthesized. NC-6300 comprises epirubicin covalently bound to polyethylene-glycol polyaspartate block copolymer through an acid-labile hydrazone bond. The conjugate forms a micellar structure spontaneously in aqueous media with a diameter of 60-70 nm. The block copolymers are partially substituted with hydrophobic benzyl groups to stabilize the micellar structure. The present study was designed to confirm that polymeric micelles incorporating epirubicin through an acid-labile linker improve the therapeutic index and achieve a broad range of therapeutic doses. Pharmacokinetic studies in rats showed highly enhanced plasma retention of NC-6300 compared with native epirubicin. The maximal tolerated doses in mice of NC-6300 and native epirubicin were 25 and 9 mg/kg, respectively, when administered three times with a 4-day interval between each dose. NC-6300 at 15 and 20 mg/kg with the same administration schedule regressed a Hep3B human hepatic tumor with slight and transient bodyweight loss. Remarkably, NC-6300 also inhibited growth of an MDA-MB-231 human breast tumor at the same dosage. In contrast, native epirubicin at 7 mg/kg administered three times with a 4-day interval was only able to slow tumor growth. Tissue distribution studies of NC-6300 showed efficient free epirubicin released in the tumor at 74% by area under the concentration-time curve (AUC) evaluation, supporting the effectiveness of NC-6300. In conclusion, NC-6300 improved the potency of epirubicin, demonstrating the advantage of NC-6300 attributable to the efficient drug release in the tumor.     

Intravesical adjuvant chemotherapy for superficial transitional cell bladder carcinoma: results of a randomized trial with epirubicin comparing short-term versus long-term maintenance treatment

PURPOSE: Intravesical instillation of epirubicin (EPI) is one of the most effective adjuvant therapies for non-muscle-invasive bladder cancer after transurethral resection. We evaluated the optimal duration of EPI instillation in a multi-institution prospective randomized clinical study. METHODS: Between June 1995 and May 1998, a total of 125 patients with superficial bladder cancer (transitional cell carcinoma grade 1 or 2) were enrolled in this study, and 102 patients were fully evaluated for recurrence. Two protocols for intravesical therapy (arm A - 30 mg EPI/30 ml saline 19 times over 1 year; arm B - 30 mg EPI/30 ml 12 times over 5 months) were established. Instillations were given every week for 4 weeks and then every 2 weeks for 4 months in arm B. After 5 months of treatment, maintenance was performed with seven further instillations (one every month for 7 months) in arm A. The analyzed background factors were the therapeutic method, gender, history (primary or recurrent tumor), stage (T classification), grade, number of tumors, and tumor size. RESULTS: There were no significant differences in the analyzed background factors between the two arms, and there were no serious side effects in the study. In an intent-to-treat analysis, the overall 3-year recurrence-free survival rates were 48.5% in arm A and 55.1% in arm B. The difference between the two groups was not significant. CONCLUSIONS: This analysis indicated that extended prophylactic maintenance instillation of EPI was not significantly effective in reducing bladder cancer recurrence.     

The effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin for prophylaxis of recurrence of superficial bladder cancer: a preliminary report

The effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin (BCG) for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were investigated in 29 patients aged a median of 70 years between January of 1991 and May of 1993. The patients received intravesical instillation of 40 mg epirubicin immediately after transurethral resection (TUR) of the bladder cancer. At 1 week after TUR, 80 mg Tokyo-strain BCG was instilled into the bladder once a week for 6 weeks. Thereafter, the patients were followed by cystoscopy and urinary cytology at 3-month intervals until recurrence was detected. Of the 29 patients, 28 had no evidence of disease over a mean follow-up period of 20 months. The 1 case of recurrence occurred at 3 months after TUR and that patient died of cancer progression. The simple recurrence rate was 3.5% after therapy. According to the person-years method, the number of recurrent tumors per 100 patient-months was 0.17. The cumulative nonrecurrence rate determined for all cases was 96.5% at 30 months. Adverse reactions, including urinary frequency, urgency, and miction pain, among others, were observed in 27 patients (93%). Only 1 patient was withdrawn from the treatment because of severe bladder-irritation symptoms due to the BCG instillation. The intravesical chemoimmunotherapy with epirubicin and BCG seemed to be effective for prophylaxis of recurrence of superficial bladder cancer.Paper presented at the 5th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 24–25 September 1993, Hakone, Japan     

UFT-E granule compliance in postoperative adjuvant chemotherapy]

UFT-E granules were administered as postoperative adjuvant chemotherapy to patients who had undergone surgery for gastric cancer, colorectal cancer or breast cancer. After treatment for one year, the dose conditions were investigated. The subjects were patients under 75 years of age in whom malignant tumors had been confirmed histologically, who had undergone curative resections, had no marked complications, and from whom personal informed consent had been obtained. As a rule, UFT-E granules were administered orally 450 mg (t.i.d.)/day continuously for one year beginning two weeks after surgery. The dose rate was studied from patient records and the tegafur blood concentrations on the 1st, 2nd, 6th, 8th and 12th month. The appearance of complications or clinical lab test abnormalities was also checked. A total of 19 cases were compliant among the 5 gastric cancer, 10 colorectal cancer, and 7 breast cancer patients. The mean administration period was 459 days (29-879 days), and the mean completion rate was 92.5%. The complications in 4 cases (21.1%) were relatively mild. A comparison of the prescribed dosage and patient records revealed a mean dose rate of 86.3%. From these findings, long-term administration of UFT-E granules with mild side effects is considered feasible. However, to achieve high compliance, it is considered necessary to gain a clear picture of dose conditions from patients records and other sources.     

Comparison of the prophylactic usefulness of epirubicin and doxorubicin in the treatment of superficial bladder cancer by intravesical instillation: a multicenter randomized trial

A multicentric randomized trial was conducted for the purpose of investigating the prophylactic efficacy of intravesical epirubicin instillation following transurethral resection of superficial bladder cancer in comparison with the efficacy of doxorubicin. The patients were centrally randomized into 2 groups and received 19 intravesical instillations of epirubicin or doxorubicin at 30 mg/30 ml physiological saline twice a week for 4 weeks and then once monthly for 11 months. A total of 150 patients with Ta and T1 superficial bladder cancer were entered in the trial, and 114 were evaluable. The nonrecurrence rates determined for each group at 1 and 2 years by the Kaplan-Meier method were 92.8% and 88.6%, respectively, for the epirubicin group and 86.4% and 81.7%, respectively, for the doxorbicin group. The differences between the two groups were not statistically significant. The main side effects encountered in this study were symptoms of bladder irritation such as micturitional pain, pollakisuria, and hematuria. The respective frequencies of those symptoms were 10%, 15.0%, and 5.0% in the epirubicin group and 14,8%, 14.8%, and O in the doxorubicin group. These results suggest that epirubicin is a useful drug, comparable with doxorubicin, for intravesical instillation chemotherapy in the prophylactic treatment of superficial bladder cancer.Paper presented at the 5th International Conference on Treatment of Urinary Tract Tumors with Adriamycin/Farmorubicin, 24–25 September 1993, Hakone, Japan     

联合灌注预防浅表性膀胱肿瘤术后复发的临床观察

 目的 了解联合膀胱腔内灌注化疗方案对预防浅表性膀胱癌复发的疗效，探讨一种理想的膀胱腔内灌注方法。方法 将45例(男性34例，女性11例)年龄在31～80岁(平均56．1岁)浅表性膀胱癌患者随机分为A、B和C3组。A组接受单次表阿霉素灌注作为对照，B、C组接受不同的羟基喜树碱和丝裂霉素C序贯膀胱腔内灌注联合用药方案。结果 A、B、C组平均随访时间分别为26．6月、36．73月、24．31月，复发率分别为54．5％(6／11)、27．7％(5／18)、6．25％(1／16)。结论 羟基喜树碱和丝裂霉素C合理地联合应用能取得较好疗效。     

Influence of alternate sequences of epirubicin and docetaxel on the pharmacokinetic behaviour of both drugs in advanced breast cancer.

BACKGROUND: Previously we observed a pharmacokinetic interference of epirubicin elimination when paclitaxel is given in combination in a sequence-dependent manner (i.e. when paclitaxel is administered as first drug). The aim of this study was to determine whether these sequence-dependent pharmacological effects were also evident when epirubicin was combined with docetaxel. PATIENTS AND METHODS: Patients who received epirubicin 75 mg/m2 or 90 mg/m2 as an intravenous bolus followed immediately by docetaxel 70 mg/m2 or 80 mg/m2 over a 1-h infusion, or the opposite sequence, every 3 weeks were eligible for this study. The pharmacokinetics of docetaxel, epirubicin and its metabolites were studied at the first and second cycle of treatment. Pharmacokinetic data were normalised to the lower dose of each drug. Toxicity was recorded at nadir and graded according to National Cancer Institute Common Toxicity Criteria. RESULTS: Twelve consecutive patients, each acting as their own control, entered the study. The sequence of drug administration of docetaxel and epirubicin did not affect the pharmacokinetics of the parent anthracycline. Statistically significant lower glucuronidation metabolism of epirubicin was observed in patients who received docetaxel before epirubicin. The pharmacokinetics of docetaxel were not influenced by the sequence of drug administration. No difference in haematological and non-haematological toxicity was observed in the two sequences of treatment. CONCLUSIONS: The pharmacokinetics of the parent anthracycline and of docetaxel were similar between the two schemes of treatment. The metabolic variations observed, i.e. differences in the plasma levels of epirubicin glucuronides, seem not to have clinical relevance.     

Analysis of risk factors of drug-induced lung injury in patients receiving gemcitabine treatment

Gemcitabine hydrochloride is a very safe medicine that even outpatients can be administered, and the bone marrow depression that is the dose limiting factor remains moderate and does not need special treatment, although it is confirmed in most cases. Meanwhile, caution is required because there is a possibility of drug-induced lung injury and death due to high frequency, compared with the appearance rate described in the packaging insertion. We investigated the clinical background of a patient in whom drug-induced lung injury appeared, and clarified the risk factor by administering gemcitabine hydrochloride. Males, people aged 65 or over, those with a smoking history and those undergoing first-line chemotherapy treatment are at risk of drug-induced lung injury. Attention must be paid to the occurrence of drug-induced lung injury, to examining the clinical course, the chest image, and the blood test, and to do earlier detection, the offending medicine discontinuance, and beginning of the treatment.