s-1-(combination) and Lung-Diseases--Interstitial

The clinical benefit of chemotherapy and the appropriate regimen for non-small-cell lung cancer (NSCLC) patients with interstitial lung disease (ILD) remain unclear. To fulfill this unmet medical need, we conducted a phase II study to elucidate the efficacy of S-1 in combination with carboplatin (CBDCA) in NSCLC patients with ILD.. A total of 33 advanced or recurrent NSCLC patients with ILD were prospectively enrolled in this multicenter, open-label, phase II study. Every 4 weeks, CBDCA at a dose of AUC 5 on day 1 and S-1 at a dose of 80 mg/m. The median age at initiating chemotherapy was 70. Sixteen patients (48.5%) had squamous cell carcinoma histology. With respect to the types of ILD, the usual interstitial pneumonia pattern was dominant (66.7%). The median number of cycles administered was 3, and the overall response rate and disease control rate were 33.3% and 78.8%, respectively. The median progression-free survival, the median survival time and the 1-year survival rate were 4.8 months, 12.8 months and 51.4%, respectively. Acute exacerbation of ILD caused by chemotherapy was noted in 2 patients (6.1%).. This is the first prospective study designed to evaluate the efficacy of a specific chemotherapeutic regimen as the primary endpoint in patients with advanced NSCLC with ILD. The combination of S-1 with CBDCA may be a treatment option for advanced NSCLC patients with ILD (The clinical trial registration number: UMIN000011046).

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Disease-Free Survival; Drug Combinations; Female; Humans; Lung Diseases, Interstitial; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Oxonic Acid; Prospective Studies; Survival Rate; Tegafur

Interstitial lung disease (ILD) is commonly concomitant with lung cancer, and its acute exacerbation (AE) is the most serious complication in patients receiving treatment for lung cancer.. To investigate the incidence and characteristic features of AE of ILD, we conducted a retrospective study of 665 consecutive patients with lung cancer who were treated at our institute between 2008 and 2014.. Among the 665 patients, 74 (11.1%) had preexisting ILD, and 64 of them received chemotherapy. Four of the 64 patients (6.3%) had experienced AE of ILD, and two (3.1%) died of respiratory failure during first-line chemotherapy. The use of a combination of carboplatin with tegafur-gimeracil-oteracil potassium (S-1) or paclitaxel as a first-line chemotherapy for non-small cell lung cancer led to a lower frequency of AE, at 8.3% (1/12) and 9.1% (1/11), respectively. The incidence of AE rose to 12.8% (5/39) during second-line treatment, and 14 (total: 15 times) of the 64 patients (21.9%) experienced AE from the time of diagnosis to the end of treatment. The incidence of AE was 17.7% (6/34), 15.8% (3/19), 5.0% (2/40), and 4.2% (1/24) in the paclitaxel-, vinorelbine-, etoposide-, and S-1-containing regimens, respectively. No difference in clinical features and laboratory data was detected between the AE and non-AE groups.. Although this was a small retrospective study, its findings showed that S-1 and etoposide may be relatively safe options for the treatment of patients with lung cancer and concomitant ILD.

Topics: Acute-Phase Reaction; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Disease Progression; Drug Combinations; Etoposide; Feasibility Studies; Female; Humans; Incidence; Lung Diseases, Interstitial; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Paclitaxel; Respiratory Insufficiency; Retrospective Studies; Tegafur

Pre-existing interstitial lung disease (pre-ILD) increases the risk of chemotherapy-related lung injury (CRLI). However, whether the risk varies by type of anti-cancer cytotoxic agent in patients with pre-ILD is unknown. In this study, we hypothesized that S-1, an oral fluoropyrimidine agent, is associated with a smaller CRLI risk than docetaxel (DTX) and investigated these agents together with radiological evaluations of pre-ILD via pre-treatment chest computed tomography (CT).. After reviewing 234 and 352 patients who underwent evaluable chest CT within 6 months prior to the administration of S-1 or DTX, respectively, from January 2006 to October 2014, 60 and 89, respectively, of these patients with pre-ILD were retrospectively analysed.. In total, 2 persons administered S-1 (3 %) and 16 treated with DTX (18 %) developed CRLI (p = 0.007) after the initial treatment (mean, 61 days), of whom 1 and 7, respectively, died because of respiratory failure. Pre-treatment CT revealed that 9 S-1-treated patients (16 %) and 15 DTX-treated patients (17 %) had pre-ILD occupying more than 25 % of the lung field. Multivariate analysis demonstrated that DTX administration increased the risk of CRLI by 6.47-fold versus S-1 therapy (p = 0.016). Of note, the area occupied by pre-ILD was also associated with the risk of CRLI (<25 %; odds ratio 0.309, p = 0.045).. Our results indicated that S-1 is associated with a smaller risk of CRLI than DTX. The area occupied by pre-ILD should also be noted when administrating anti-cancer agents.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Docetaxel; Drug Combinations; Female; Humans; Logistic Models; Lung Diseases, Interstitial; Lung Injury; Lung Neoplasms; Male; Medical Records; Middle Aged; Oxonic Acid; Predictive Value of Tests; Retrospective Studies; Risk; Taxoids; Tegafur; Tomography, X-Ray Computed

There is no established standard regimen for non-small cell lung cancer (NSCLC) patients with interstitial lung disease (ILD). For them, we performed a pilot study to evaluate the feasibility of chemotherapy with carboplatin and S-1, which are known as cytotoxic drug with rare development of ILD as adverse event.. A total of 21 chemotherapy-naive NSCLC patients with ILD were prospectively enrolled between March 2009 and September 2011. Every 3 weeks, carboplatin at a dose of AUC 5 on day 1 and S-1 at a dose of 80 mg/m2 daily for 14 days were administered.. The median age at initiating chemotherapy was 67. Histological examination revealed 10 patients (48 %) with adenocarcinoma. Before chemotherapy, partial pressure of arterial O2 (PaO2) was low with a median of 71 Torr on room air. The median number of cycles administered was four, and the overall response rate and disease control rate were 33 and 67 %, respectively. At the time of data cut-off, all patients were deceased. The median progression-free survival (PFS) and median overall survival (OS) periods were 4.2 and 9.7 months. There was no significant difference of PFS and OS according to tumor histology. Acute exacerbation (AE) of ILD following S-1 plus carboplatin occurred in two patients (10 %, 2/21) within first course treatment. However, they were successfully managed with steroid therapy and survived for 7.0 and 8.8 months, respectively, after AE-ILD development.. This is the first prospective study to evaluate the safety and efficacy of S-1 plus carboplatin treatment for NSCLC patients with ILD. This regimen could be a feasible option for NSCLC patients with ILD, regardless of tumor histology. Our results would support to carry out a large-scale clinical trial to confirm the feasibility of this regimen.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Drug Combinations; Female; Humans; Kaplan-Meier Estimate; Lung Diseases, Interstitial; Lung Neoplasms; Male; Middle Aged; Oxonic Acid; Pilot Projects; Prospective Studies; Tegafur

We report a case of lethal interstitial pneumonia that occurred after neoadjuvant chemotherapy for advanced gastric cancer. A 76-year-old man with no history of interstitial pneumonia received 2 courses of S-1 (100 mg/body) following 1 course of S-1 plus cisplatin( CDDP) from June 2012. He complained of dyspnea on exertion 6 days after completion of the treatment. Chest radiography and computed tomography (CT) revealed diffuse interstitial lesions in bilateral lung fields. Bronchoalveolar lavage( BAL) revealed an increased number of lymphocytes and leukocytes. Transbronchial lung biopsy (TBLB) revealed interstitial pneumonia with fibrous thickening in the alveolar septum. The drug lymphocyte stimulation test (DLST) was positive for S-1 and negative for CDDP. These results suggested that S-1 had induced interstitial pneumonia. Steroid therapy( 40 mg/day prednisolone following 500 mg methylprednisolone pulse therapy) and an antibiotic agent were administered but were ineffective. He rapidly developed respiratory failure and required tracheal intubation and mechanical ventilation on hospital day 24, and died on hospital day 38.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Drug Combinations; Fatal Outcome; Humans; Lung Diseases, Interstitial; Male; Neoadjuvant Therapy; Oxonic Acid; Stomach Neoplasms; Tegafur

The patient was a 77-year-old woman admitted for nausea and abdominal pain. Computed tomography (CT) revealed advanced ascending colon cancer with liver metastasis. After operation, we started combination chemotherapy of S-1 and irinotecan (CPT-11); S-1(80 mg/m²) administered orally for consecutive days followed by 14 days rest.CPT -11 (100 mg/m²) was given as a 2-hour infusion on day 1 and 15. The patient complained of high fever and subsequent dyspnea with severe hypoxemia after the first course of combination chemotherapy of S-1 and CPT-11.CT scan showed diffuse interstitial lesions with ground glass opacity on both lungs. Steroid pulse therapy with oxygen therapy remarkably improved her symptoms, and abnormal findings on CT scan also resolved. Drug lymphocyte stimulation test was positive against S-1 and negative against CPT-11. These findings were consistent with S-1-induced lung injury. Drug -induced pneumonia needs to be considered in the differential diagnosis when patients treated with S-1 and CPT-11 combination therapy present high fever and dyspnea.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Combinations; Fatal Outcome; Female; Humans; Irinotecan; Lung Diseases, Interstitial; Neoplasm Staging; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

S-1, an oral fluoropyrimidine derivative, has been identified as an effective agent for the treatment of breast cancer. We present here a case of interstitial pneumonitis that occurred after S-1 treatment. A n 80-year-old woman was diagnosed with stage III infiltrating ductal carcinoma of the left breast and underwent a modified radical mastectomy in November 2001, followed by six courses of paclitaxel. In October 2008, metastatic disease was detected in her skeletal system. Therefore, S-1 chemotherapy was initiated (100 mg/body). Five days after starting S-1, she developed severe eruptions along with dyspnea. X-rays and CT scan showed diffuse ground glass shadow. Both her symptoms and the radiographic findings resolved dramatically after the start of high-dose corticosteroid therapy. Clinicians should be aware that S-1 has the potential to cause lung injury when it is included in chemotherapy.

Topics: Aged, 80 and over; Breast Neoplasms; Drug Combinations; Female; Humans; Lung Diseases, Interstitial; Neoplasm Metastasis; Oxonic Acid; Tegafur; Tomography, X-Ray Computed

A 67-year-old man with multiple liver metastases of colonic cancer was treated with combination therapy of S-1 and irinotecan (CPT-11): S-1 (120 mg/day) administered orally for 14 consecutive days followed by 14 days rest. CPT-11 (100 mg/m(2)) was given as a 2-hour infusion on day 1 and 15. The patient complained of high fever and subsequent exertional dyspnea in the middle of the second course of S-1/CPT-11 therapy. He was hospitalized with severe hypoxemia. CT scan showed extensive ground glass and consolidative changes in bilateral lungs. Steroid pulse therapy with oxygen therapy remarkably improved his symptoms, and abnormal findings on CT scan also resolved. Drug-induced pneumonia needs to be considered in the differential diagnosis when patients treated with S-1/CPT-11 combination therapy present high fever and dyspnea.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Camptothecin; Colonic Neoplasms; Drug Combinations; Humans; Irinotecan; Liver Neoplasms; Lung Diseases, Interstitial; Male; Oxonic Acid; Tegafur; Tomography, X-Ray Computed; Treatment Failure

An 80-year-old man with no history of thoracic radiotherapy nor interstitial pneumonia was administered S-1 for gastric cancer in June 2007. Twenty-two days after starting S-1, he had dyspnea, and X-rays showed reticular shadows in both lung fields, yielding a diagnosis of interstitial pneumonia. Drug lymphocyte stimulating test (DLST) was positive against S-1. The total dose of S-1 was 2,200 mg to the symptom onset. We immediately started steroid pulse therapy after emergency hospitalization, and it revealed improved condition and he was able to leave the hospital. S-1 administration is becoming frequent because RCTs supported the efficacy of S-1 for gastric cancer. Interstitial pneumonia as a side effect of S-1 is not frequent, but it is necessary to pay attention to dyspnea throughout the duration of administration.

Topics: Aged, 80 and over; Drug Combinations; Humans; Lung Diseases, Interstitial; Male; Oxonic Acid; Stomach Neoplasms; Tegafur; Tomography, X-Ray Computed

A 37-year-old female with advanced gastric cancer and liver metastases was treated with S-1. Since the patient noticed a transient cough and low-grade fever in the middle of the third course of treatment, administration of S-1 was discontinued. Her symptoms resolved in three days, and the fourth course was started again. However, two weeks later she was hospitalized with non-productive coughing, and exertional dyspnea with severe hypoxemia. CT scan showed minimal ground glass shadow in bilateral lungs and that the multiple liver metastases were strikingly reduced in size. CT scan obtained on the third hospital day showed extensive ground glass and consolidative changes in bilateral lungs. She died on the same day despite high-dose steroid therapy. Although a definite causal relationship between pneumonia and S-1 is still unproven, S-1-induced pneumonia needs to be considered in the differential diagnosis when patients present with dyspnea are treated with S-1.

Topics: Adult; Antimetabolites, Antineoplastic; Diagnosis, Differential; Drug Combinations; Dyspnea; Female; Humans; Liver Neoplasms; Lung Diseases, Interstitial; Lymph Nodes; Lymphatic Metastasis; Oxonic Acid; Stomach Neoplasms; Tegafur

A 76-year-old male patient was diagnosed with advanced double cancer of the lung and stomach. He had also been suffering from interstitial pneumonitis for several years. He was treated with combination of cisplatin and TS-1. TS-1 (120 mg/body/day) was administered for 21 days from day 1, and cisplatin (60 mg/m(2)) was given on day 8 followed by a 14-days interval. After two courses of chemotherapy,the dose of cisplatin was reduced to 48 mg/m(2) because of grade 1 serum creatinine elevation. The lesions of the lung and stomach were improved significantly without exacerbation of the interstitial pneumonitis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Drug Administration Schedule; Drug Combinations; Humans; Lung Diseases, Interstitial; Lung Neoplasms; Male; Neoplasms, Multiple Primary; Oxonic Acid; Remission Induction; Stomach Neoplasms; Tegafur

A newly approved oral fluoropyrimidine, TS-1, is a dihydropyrimide dehydrogenase (DPD)-inhibiting fluoropyrimidine (DIF) drug. We describe a case of interstitial pneumonia probably caused by TS-1. A peripheral blood lymphocytes stimulating test (DLST) with TS-1 demonstrated a substantial positive reaction. So far only three cases of TS-1-induced interstitial pneumonia have been reported but the relationship between interstitial pneumonia and TS-1 was demonstrated only in this case. Considering that interstitial pneumonia has also been reported with 5-FU, it is necessary in the future to clarify which component of this drug is directly related to interstitial pneumonia.

Topics: Adenocarcinoma; Aged; Antimetabolites, Antineoplastic; Drug Combinations; Humans; Lung Diseases, Interstitial; Male; Oxonic Acid; Pyridines; Stomach Neoplasms; Tegafur