Incidence Of Pulmonary Toxicity Research Articles

Efficacy and Toxicity of Stereotactic Body Radiation Therapy Treatment of Multiple Lung Lesions

<h3>Purpose/Objective(s)</h3> As the role of SBRT in caring for patients with complex cancer presentations continues to expand, it is paramount to elucidate how many courses of lung SBRT are safe and what factors predict toxicity. Our study seeks to evaluate the dose-volume factors and associated toxicities for treatment of multiple lung tumors with SBRT. <h3>Materials/Methods</h3> This retrospective IRB approved study was conducted using our institutional database of patients who underwent SBRT for multiple lung lesions between 2012 to 2020. 64 patients underwent SBRT for multiple tumors for a total of 137 tumors treated. We compared dosimetry and clinical outcome parameters of these patients to a paired set of 50 randomly selected patients who received SBRT for a solitary lung lesion. Variables collected include patient age, gender, cancer stage, tumor histology, SBRT dose, dosimetric parameters, toxicities from SBRT, and progression-free survival (PFS). Acute toxicity was defined as any toxicity related to lung SBRT occurring <90 days from the start of SBRT and late toxicity was beyond 90 days from the end of SBRT. Statistical analysis was performed using statistical software. <h3>Results</h3> 137 pulmonary lesions in 64 patients (2+ lesions in every patient) were treated using SBRT at our institution. Of these 137 lesions, 122/137 (89.1%) were primary lung tumors and 15/137 (10.9%) were metastatic lesions. Out of the 137 lesions, 9.5% were classified as SCLC, 43.1% as adenocarcinoma, 36.5% as squamous cell carcinoma, and 10.9% as distant metastases. The mean prescription dose for multi-lesion patients was 50 Gy delivered in 3-5 fractions versus 50 Gy in 5 fractions in the single lesion group. The mean V5 (47.3% vs. 25.7%, p<0.05), V10 (26.8.3% vs. 15.4%, p<0.05), V20 (10.2% vs. 4.5%, p<0.05), and mean lung dose (10.05 Gy vs. 5.29 Gy, p<0.05) were significantly greater in multi-lesion patients compared to single lesion patients, respectively. Fatigue and dyspnea were the most commonly reported acute toxicities; 56.2% multi-lesion patients experienced fatigue and 18.8% experienced dyspnea while 22.0% of single lesion patients experienced fatigue and 12.0% experienced dyspnea (p=0.315). No late toxicities were documented. 126/137 (92.0%) of the lung lesions treated with multiple SBRT treatments demonstrated local control, while 11/137 (8.0%) had local recurrence. 1-year PFS was 92.2% in the multi-lesion group versus 84.0% in the single lesion group. There was no significant correlation between pulmonary toxicity and histology in the single lesion and multi-lesion groups. <h3>Conclusion</h3> Our results suggest that SBRT treatment of multiple pulmonary tumors is safe and feasible without increasing in acute or late pulmonary toxicity. While there is significant difference in all lung parameters between these two groups, it did not translate into increasing toxicity. Further studies are needed to understand the relation between radiation dose parameters and incidence of pulmonary toxicity.

The Risk-Benefit Balance of Treatments for Hodgkin Lymphoma Reported in the Randomised and Non-Randomised Trial Setting: A Systematic Review

Introduction: Hodgkin lymphoma (HL) is a cancer that originates in the lymphocytes. Current standard of care (SOC) therapies include combination chemotherapy and/or radiotherapy regimens. However, optimising treatment to obtain high efficacy with low toxicity remains a challenge. A systematic literature review (SLR) was conducted to identify relevant clinical evidence for front line treatments in the management of patients with advanced Hodgkin lymphoma (HL) (defined as stage IIb, III, and IV).Methods: A SLR was performed in July 2016 to summarise the efficacy and safety of front-line treatments for the management of patients with advanced HL.Results: In total, 70 unique studies, 38 randomised controlled trials (RCTs) and 32 non-RCTs, were identified and included in the review. Of the 38 included RCTs, nine were open-label trials, while the remaining 29 trials did not report details of blinding. Most patients with advanced HL reported durable remissions following front-line SOC treatment (ABVD and escBEACOPP) (Table 1); however, these treatment options are associated with adverse events. Further, up to 30% of advanced HL patients relapse after frontline treatment, indicating an unmet need for new therapies. The incidence of secondary malignancy at long-term follow-up after HL treatment remains a major adverse effect. Nine of the included studies reported secondary malignancy in 1.7-8.3% of patients, with acute myeloid leukaemia and non-Hodgkin lymphoma the most commonly observed secondary malignancies. However, the follow-up across these studies ranged from 5 to 8 years and the incidence of secondary malignancy are potentially underestimated due to limited follow-up. A single study reported that the cumulative incidence of secondary malignancies was 48.5% at 40 years follow-up. The risk of secondary malignancy was increased in patients receiving combined modalities compared with chemotherapy or radiotherapy alone and the risk is greater in men compared with women. The risk of second malignancy increases after initial therapy and remains elevated at ≥35 years after treatment. In the majority of studies radiotherapy was administered either as adjuvant or consolidation therapy. The most commonly reported adverse effects observed in patients receiving radiotherapy were nausea/vomiting, infections, secondary malignancy, and toxicities related to cardiovascular and pulmonary systems. Pulmonary toxicity was reported in up to 36% of patients across 23 studies with bleomycin-containing regimens. Discontinuation or dose reduction of bleomycin was associated with a decrease in the incidence of pulmonary toxicity; however, the impact of bleomycin dose reductions on efficacy outcomes was not statistically significant. Neutropenia and febrile neutropenia are also dose-limiting events that occur during chemotherapy in patients with malignant lymphoma. Granulocyte colony-stimulating factor, a haematopoietic growth factor which prevents neutropenia/febrile neutropenia, was used for primary or secondary prophylaxis in 7 and 5 of the studies included in the SLR, respectively.Conclusion: Failure rates of up to 30% and serious adverse events are reported following treatment with current standard of care therapies in newly diagnosed patients with advanced HL. Therefore, there exists an unmet medical need for an effective and well-tolerated therapy in HL. [Display omitted] DisclosuresDalal:Takeda Pharmaceuticals International Co: Employment, Equity Ownership. Mitchell:DRG Abacus: Employment. McCloskey:DRG Abacus: Employment. Zagadailov:Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Employment. Gautam:Takeda Pharmaceuticals International Co: Employment, Equity Ownership.

Preparation and In Vitro Evaluation of Alginate Microparticles Containing Amphotericin B for the Treatment of Candida Infections.

Invasive candidiasis (IC) remains as a major cause of morbidity and mortality in critically ill patients. Amphotericin B (AmB) is one of the most effective antifungal agents commonly used to treat this infection. However, it induces severe side effects such as nephrotoxicity, cardiac alterations, nausea, fever, and liver damage. The utilization of drug delivery systems has been explored to overcome these limitations. Several AmB lipid formulations have been developed and are currently available in the market. Although they have the ability to reduce the main side effects of free AmB, their high cost, necessity of repeated intravenous injections for successful treatment, and incidence of pulmonary toxicity have limited their use. In the last decades, alginate has gained significant interest in drug delivery applications as a cost-effective strategy to improve the safety and therapeutic effect of toxic drugs. In this work, the clinically relevant drug AmB was encapsulated into alginate microparticles using the emulsification/external gelation method. We hypothesize that this synthesis strategy may positively impact the antifungal efficacy of AmB-loaded MCPs toward Candida albicans cells while reducing the toxicity in human lung cells. To prove this hypothesis, the ability of the microplatform to disrupt the cellular membrane potential was tested and its antifungal effectiveness toward Candida albicans cells was evaluated using the cell counting and plate count methods. Moreover, the toxicity of the microplatform in human lung cells was evaluated using CellTiter 96® AQueous cell viability assay and qualitative diffusion analysis of acridine orange. Our results demonstrated that the platform developed in this work was able to induce antifungal toxicity against Candida albicans yeast cells at the same level of free AmB with minimal toxicity to lung cells, which is one of the main side effects induced by commercial drug delivery systems containing AmB. Overall, our data provides convincing evidence about the effectiveness of the alginate-based microplatform toward Candida albicans cells. In addition, this vehicle may not require several infusions for a successful treatment while reducing the pulmonary toxic effect induced by commercial lipid formulations.

Real-world incidence of grade III/IV side effects, emergency room visits, and hospital admissions after treatment with adjuvant durvalumab in locally advanced non-small cell lung cancer.

e19276 Background: Durvalumab is a selective human IgG1 monoclonal antibody that blocks PD-L1 binding to PD-1 and CD80, allowing T cells to recognize and kill tumor cells. Durvalumab is FDA approved for adjuvant treatment of locally advanced unresectable NSCLC after definitive chemoradiation based on data presented in the PACIFIC trial with benefit in PFS and overall survival. In the PACIFIC trial, discontinuation of the durvalumab because of adverse events occurred in 15.4% of the patients. The most frequent adverse events leading to its discontinuation were pneumonitis (4.8%), radiation pneumonitis (1.3%), and pneumonia (1.1%). The aim of our study is to review real world single institution experience of durvalumab in locally advanced NSCLC. Methods: 23 patient charts with locally advanced NSCLC who had durvalumab ordered for adjuvant treatment were reviewed. 4 patients were excluded given failure to start durvalumab or lack of complete records with treatment at outside institutions. Results: 19 patients were included in the final analysis. 18/19 patients received definitive chemoRT and 1 patient received definitive RT alone given co-morbidities. 8 patients finished durvalumab and 4 are currently on treatment. 8/19 patients (42.1%) had Grade III/IV side effects reported. 7/19 (36.8%) patients had durvalumab discontinued. In 6 patients (31.5%), durvalumab was discontinued due to Grade III/IV toxicity (all with pneumonitis) while 1 patient had sepsis with disease progression. 2 patient had died with one patient death related to pneumonitis/pneumonia along with underlying co-morbidities and the second patient with disease progression. 4 patients (21%) had 7 ER visits and 5 patients (26%) were admitted to the hospital for various reasons 7 times. 2 patients required higher level of care in the step down unit. Treatment was delayed only twice in all 19 patients because of a clinical reason. Conclusions: Durvalumab is an exciting new development in the treatment of locally advanced NSCLC. Our review revealed higher than previously reported incidence of pulmonary toxicity as well as higher discontinuation rate. Other than pulmonary toxicity, durvalumab is very well tolerated with low incidence of ER visits, hospital admissions and treatment delays. Clinicians should monitor patients very closely for pulmonary toxicity during durvalumab treatment. Regular pulmonary function testing may be a reasonable approach to monitor the patients on durvalumab.

Delivery of bleomycin among patients with testicular cancer: A population-based study of pulmonary monitoring and toxicity.

e16056 Background: Bleomycin is commonly used to treat testicular cancer and can be associated with severe pulmonary toxicity. There is limited information about how clinicians monitor patients during treatment and the incidence of pulmonary toxicity in routine practice. Methods: The Ontario Cancer Registry was linked to electronic records of treatment to identify all incident cases of testicular cancer treated with orchiectomy and bleomycin, etoposide, and cisplatin (BEP) chemotherapy in the province of Ontario during 2005-2010. Health-administrative databases were used to describe use of pulmonary function tests (PFTs), chest imaging and physician visits. Results: 475 patients were treated with orchiectomy and chemotherapy. Complete chemotherapy records were available for 93% (368/394) of men treated with BEP. Bleomycin was omitted among 32% (116/368) of patients. PFTs were performed in 17% (63/368), 17% (61/368) and 29% (106/368) of patients before BEP, during BEP, and within 2 years of finishing BEP, respectively. During chemotherapy, 62% of patients (227/368) had chest imaging. In the two years following BEP, 23% (85/368) had a physician visit for respiratory symptoms; this rate was substantially higher among men with greater exposure to bleomycin; 40% (24/60) for 10-12 doses bleomycin vs 21% (53/250) for 7-9 doses vs 14% (8/58) for 1-6 doses (p = 0.002). Two percent of men (8/368) had visit codes for pulmonary fibrosis. Conclusions: A substantial proportion of men treated with BEP will seek medical attention after chemotherapy for respiratory symptoms and this is associated with cumulative dose of bleomycin. Use of PFTs and chest imaging during treatment is common. Whether PFT test results or clinical symptoms are leading to bleomycin dose omission is uncertain.

Effect of dose rate on pulmonary toxicity in patients with hematolymphoid malignancies undergoing total body irradiation

BackgroundThis study evaluated the effect of radiation dose rate in patients with hematolymphoid malignancies undergoing myeloablative conditioning with total body irradiation (TBI), for hematopoietic stem cell transplantation.MethodsThe incidence of pulmonary toxicity (PT) and treatment efficacy were compared between the conventional (≥ 6 cGy/min) and reduced dose rate (< 6 cGy/min). Seventy-seven patients receiving once-daily TBI between 2000 and 2016 were reviewed. We compared the cumulative rate of PT, overall survival (OS), relapse, and transplantation-related mortality (TRM) between conventional (n = 54) and reduced (n = 23) groups. Factors associated with PT were assessed in the presence of competing risks.ResultsThe median follow-up time was 40.7 months, and PT occurred in 50 patients (64.9%). On multivariate analyses, the groups classified by the dose rate (P = 0.010), total dose (P = 0.025), and conditioning regimen (P = 0.029) were significant factors for the development of PT. OS was significantly reduced when PT occurred (P < 0.001). However, the OS, relapse, and TRM were not different between the two groups.ConclusionsIn summary, about two-thirds of the patients undergoing daily TBI experienced PT, which affected OS. Therefore, reducing the dose rate (less than 6 cGy/min) of TBI can decrease the risk of PT, without compromising the treatment efficacy.

Impact of bleomycin (BLM) administration on the development of pulmonary toxicity in advanced germ cell tumors (GCT) receiving first-line chemotherapy (CT): A meta-analysis of randomized studies.

482 Background: Little is known about the impact of BLM administration on the development of pulmonary toxicity (PT) in patients (pts) with advanced GCT. This information is critical to further enhance the successful delivery of effective and safe CT in these pts. Methods: Literature was searched for randomized trials of 1st-line CT ( ≥ 3 cycles) for GCT. Descriptive statistics were used to summarize data, dichotomized by BLM-containing vs non containing CT. Univariable and multivariable analyses by random effect models evaluated the predictive role of BLM administration on the development of all grade and G3-4 PT, adjusted for the length of follow-up (FUP, continuous), time-frame of treatment ( ≤ 1997 versus &gt; 1997) % of pts with lung metastases (LM), % of primary mediastinal GCT (PMGCT), IGCCCG risk group. Results: 53 arms of 26 phase II and III trials totalling 6,498 pts were selected: 40 with BLM (n = 5,093) and 13 without BLM (n = 1,405). Median % of pts with LM was 44% (range 22-84%) and 31% (19-79%) in BLM-containing and non containing arms (Wilcoxon test p = 0.505). Median % of PMGCT was 15% (range 0-48%) and 2% (0-13%), respectively (p = 0.146). Median BLM total dose and No. of administrations were 360mg (range 120-375) and 12 (2-24). Median FUP was 52 and 53 months, respectively. The pooled probability of all grade PT was 11.7% (95% CI: 8.4-16.0%) and 1.7% (95% CI: 0.7-4.2%) in BLM-containing and non containing arms. Univariably, BLM administration was associated with the incidence of both all grade (odds ratio [OR]: 7.57, 95%CI: 2.84-20.18, Wald test p &lt; 0.001) and G3-4 PT (OR: 5.19, 95%CI: 1.57-17.16, p = 0.007). Multivariably, BLM administration was significantly associated with the incidence of all grade PT (OR: 4.14, 95%CI: 1.36-12.59, p = 0.012) and trended to significance for G3-4 toxicity (OR: 2.24, 95%CI: 0.91-5.51, p = 0.080). Conclusions: In this meta-analysis, BLM administration was significantly associated with the development of PT in pts with GCT. The quantification of the magnitude of incidence of PT provided here might be useful to optimize the delivery of non-PEB CT in the 1st-line setting.

Factors Influencing Pulmonary Toxicity in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation in the Setting of Total Body Irradiation-Based Myeloablative Conditioning

This study evaluated factors associated with increased risk of pulmonary toxicity (PT) from any cause in pediatric patients after myeloablative conditioning, using total body irradiation (TBI), followed by allogeneic hematopoietic stem cell transplantation (HSCT). The records of 129 consecutive pediatric patients (range: 1-21 years of age) who underwent TBI-based myeloablative conditioning for hematologic malignancies at our institution between January 2003 and May 2014 were reviewed. Although total TBI doses ranged from 10.5 to 14 Gy, lung doses were limited to 10 Gy with partial transmission blocks. TBI dose rates ranged from 5.6 cGy/min to 20.9 cGy/min. PT was classified using clinical symptoms, radiographic evidence, and ventilatory defects on pulmonary function tests. Noninfectious (idiopathic) pneumonia syndrome (IPS) was characterized by patients exhibiting PT while demonstrating no signs of infection throughout the follow-up period. PT from any cause developed in 70.5% of patients and was significantly associated with increased transplantation-related mortality (TRM) (P=.03) and decreased overall survival (OS) (P=.02). IPS developed in 23.3% of patients but was not associated with increased TRM (P=.6) or decreased OS (P=.5). Acute graft-versus-host disease (GVHD) significantly affected PT (P=.001) but did not significantly influence the development of IPS (P=.4). Infection was a leading cause of PT (75.8%). TBI dose rate significantly affected development of overall PT (P=.02) and was the sole factor to significantly influence the incidence of IPS (P=.002). TBI total dose, dose per fraction, disease type, transplantation chemotherapy, age of patient, sex, and donor type did not significantly impact overall PT or IPS. A high incidence of PT was noted in this large series of homogeneously treated pediatric patients undergoing TBI for allogeneic HSCT. TBI dose rates affected overall PT and strongly influenced IPS. TBI dose rate is a contributing factor influencing pulmonary toxicity and rates less than 15 cGy/min should be considered to decrease the risk of IPS.

Incidence and risk of pulmonary toxicity in patients treated with mTOR inhibitors for malignancy. A meta-analysis of published trials

Background. mTOR inhibitors are currently used in the treatment of solid malignancies. Since their approval, several cases of pulmonary toxicity (PT) have been described. This analysis aims to report the incidence and the risk of PT in published randomized controlled trials. Material and methods. PubMed and Scopus were reviewed for phase II–III randomized controlled trials with temsirolimus and everolimus. The characteristic of each study and incidence of all- and high-grades PT were collected. Results. A total of 2233 patients were available for meta-analysis: 989 had breast cancer, 833 had neuroendocrine tumor and 411 had metastatic renal cell carcinoma. In patients taking mTOR inhibitors, the incidence of all- and high-grades PT was 10.4% and 2.4%, respectively. Compared to controls, the relative risk for all- and high-grades PT was 31- and 8.8-folds, respectively. No significant heterogeneity was observed between the studies. Not any relationship was found between the incidence of lung metastases, treatment exposure and the incidence of PT. Conclusions. The high grade PT is a rare event and 10% of patients may experience mild grade toxicity with a worsening of quality of life and interruption of therapy in some cases. We recommend monitoring of PT in patients treated with mTOR inhibitors.

Multicenter phase II study of concurrent high-dose (72Gy) three-dimensional conformal radiotherapy (3D-CRT) without elective nodal irradiation with chemotherapy using cisplatin and vinorelbine for unresectable stage III non-small cell lung cancer (NSCLC).

7070 Background: The optimal dose of radiotherapy remains unclear in concurrent chemoradiotherapy for unresectable stage III NSCLC. We previously concluded that the recommended dose for further trial was 72Gy in a phase I study (Sekine et al., Int J Radiat Oncol Biol Phys. 953-959, 2012). Methods: Eligible patients (unresectable stage III NSCLC, age between 20 and 74, PS 0-1, V20 ≤ 30%) received cisplatin (80 mg/m2 day 1) and vinorelbine (20 mg/m2 days 1 and 8) repeated every 4 weeks for 3-4 cycles. The 3D-CRT started at the first day of chemotherapy at a total dose of 72 Gy in 36 fractions. The primary endpoint was a 2-year survival rate and the planned sample size was 60 to reject the rate of 45% under the expectation of 65% with a power of 90% and an alpha error of 5%. Results: Thirty-one patients from 4 institutions were enrolled between May 2009 and March 2010. This trial was terminated early due to slow accrual and grade 5 pulmonary toxicities in 2 patients. There were 25 men and 6 women with a median (range) age of 59 (32-72) years. Of these, 23 had adenocarcinoma and 21 had stage IIIA disease. The median (range) V20 value was 20 (9-30). The full planned dose of radiotherapy could be administered in 30 (97%) patients, and 26 (84%) of the patients received 3-4 cycles of chemotherapy. During the chemoradiotherapy, grade 3-4 febrile neutropenia, infection and esophagitis were noted in 5, 4 and 1 of the 31 patients, respectively. After completion of the planned chemoradiotherapy, 5 patients had grade 3 or higher radiation pneumonitis, and 2 (6%) of these patients died at 6.6 and 7.3 months after the treatment started. The overall response rate was 97% (95% confidence interval: 83.3-99.9). Twenty-four patients are alive and thirteen patients experienced recurrence (2 had loco-regional recurrences, 7 had distant recurrence and 4 had mixed recurrence pattern) at a median follow up of 16.4 months. Conclusions: Concurrent high-dose (72Gy) 3D-CRT with chemotherapy using cisplatin and vinorelbine may have a too excessive incidence of pulmonary toxicities to warrant any further evaluation.

Impact of Preoperative Chemotherapy on Pulmonary Function Tests in Resectable Early-Stage Non-small Cell Lung Cancer

Several chemotherapy agents, including gemcitabine and paclitaxel, have been reported to cause interstitial pneumonitis. The incidence of pulmonary toxicity from the combination of gemcitabine and paclitaxel is reported to be approximately 5%. In this report, pulmonary function test (PFT) results were analyzed from two similar randomized phase 2 trials that tested platinum and nonplatinum regimens preoperatively in patients with stage I or II non-small cell lung cancer (NSCLC). The regimens included gemcitabine plus carboplatin, paclitaxel, or cisplatin. PFT and dyspnea scores were obtained at baseline and postchemotherapy, and were compared to one of several secondary end points, including ability to undergo surgical resection. Baseline PFT scores varied with smoking status. Mean levels of diffusing capacity of the lung for carbon monoxide (Dlco) adjusted for hemoglobin declined 8% from pre- to postinduction (Wilcoxon signed rank test, p < 0.0001). Changes in FVC, FEV(1), and total lung capacity were not statistically significant after chemotherapy. Although 27% of patients in the study had some reduction in PFT results, only 2 of the 85 eligible patients did not undergo surgery due to PFT reduction following chemotherapy. One patient in the study experienced a clinically significant respiratory toxicity (grade 3 dyspnea). Pulmonary toxicity was only statistically associated with male gender. In the preoperative setting, gemcitabine-based chemotherapy was well tolerated. The most commonly affected PFT parameter postchemotherapy was the Dlco. Although 15% of patients had a significant reduction in the Dlco postchemotherapy, it did not correlate with clinical symptoms or affect the ability to undergo surgical resection.

Radiation-induced Pulmonary Toxicity and Related Risk Factors in Breast Cancer

Purpose: This study was designed to assess the incidence of pulmonary toxicity (PT) and related risk factors in breast cancer patients treated with postoperative adjuvant radiotherapy (RT) with or without the use of chemotherapy. Methods: The whole breast or chest wall was irradiated with two tangential photon fields to a total dose of 50.4 Gy in 261 patients. A single anterior oblique photon field for a supraclavicular (SCL) node included if indicated. All patients underwent threedimensional RT planning (3D RTP), and the calculation of dose volume histogram (DVH) parameters (i.e., ipsilateral lung volume that received ≥15 Gy [V15], V20, V30, and mean lung dose [MLD]). The relationship of symptomatic radiation pneumonitis (SRP) and pulmonary toxicity as discerned by radiographic features (radiographic pulmonary toxicity or RPT) with the clinical and DVH parameters were evaluated. In addition, the relationship of severity of RPT with the DVH parameters was assessed. Results: SRP and RPT developed in 1.9% (5/261) and 22.6% (59/261) of patients, respectively. Age (p=0.008), inclusion of an SCL field (p<0.0001), use of chemotherapy (p<0.0001), use of taxane (p<0.0001), and all DVH parameters (p<0.0001) were associated with RPT in univariate analysis. Based on the results of multivariate analysis, V 30 (p<0.001), age (p=0.001) and use of taxane (p=0.036) were significant risk factors in the development of RPT. None of the DVH parameters was associated with the severity of RPT. Conclusion: The incidence rate of SRP was very low and there was no correlation between any clinical factor or DVH parameters and SRP. Age, the use of taxane-based chemotherapy and V 30 were correlated with the development of RPT.

Pulmonary toxicity of cytotoxic agents: A meta-analysis

19573 Background: Pulmonary toxicity is one of the most serious adverse effects of cytotoxic agents, and affected patients require discontinuation of the anti-cancer therapy, and it even proves fatal in many cases. Its incidence, however, may be considerably biased, as it may be influenced by many factors such as intercurrent medications or co-morbidities. The purpose of our study was to evaluate the incidences of pulmonary toxicity by cytotoxic agents in published data relating to prospective randomized comparative studies. Methods: A Medline literature search was conducted to extract prospective randomized comparative studies (either phase II or III) that included docetaxel, paclitaxel, irinotecan, vinorelbine and gemcitabine. Comparisons had to be performed between regimens with and without one of these agents, in addition to best supportive care with or without other common agent(s), so as to be able to clearly attribute the toxicity to the agent. Reports lacking detailed toxicity data were excluded. Results: The table below summarizes the results of the finally evaluated 47 studies (5 to 12 per agent) fulfilling the criteria. As many studies showed no pulmonary toxicity, standard statistical methods for meta-analysis were not applicable. Conclusions: The present study analyzing data in prospective randomized comparative studies might minimize bias of the relative incidence of pulmonary toxicity. Pulmonary toxicity was rarely encountered in randomized comparative studies. No increase in frequency was shown by the inclusion of any of the five cytotoxic agents. [Table: see text] No significant financial relationships to disclose.

Neoadjuvant chemotherapy with gemcitabine-containing regimens in stage I-II non-small cell lung cancer (NSCLC): Initial results of pre-operative pulmonary function testing (PFTs) in the GINEST project

7227 Background: Several chemotherapy agents including gemcitabine (Gem) and paclitaxel (Tax) have been reported to cause interstitial pneumonitis. The incidence of pulmonary toxicity from the combination of Gem-Tax is reported to be 5–10%. The GINEST Project consists of two similar randomized phase II trials testing platinum and non-platinum regimens preoperatively in patients with Stage I or II NSCLC. This report focuses on PFT analysis; additional study objectives include response and survival outcomes, as well as quality of life. Methods: The regimens in Trial 1 included Gem/carboplatin (GCb)and Gem/paclitaxel (GT); in trial 2, GCb and Gem/cisplatin (GC). PFTs and dyspnea scores were obtained pre and post chemotherapy (chemo) to assess one of several secondary endpoints: drug-induced pulmonary injury and effect on ability to undergo surgical resection. Results: Pre and post chemo PFT data was available in 42/54 pts in trial 1 and in 20/28 pts in trial 2. In this combined group of 62 pts, the diffusing...

Insidious Onset of Amiodarone Pulmonary Toxicity Presented with Hemoptysis

Amiodarone is widely used to control fatal arrhythmia. However, amiodarone therapy is associated with a relatively high incidence of pulmonary toxicity, up to 5 to 10%. Typical symptoms are nonspecific and often manifest as nonproductive cough, dyspnea and interstitial infiltrates in patients with acute pneumonitis or chronic fibrosis. However, hemoptysis is a very rare symptom of amiodarone pulmonary toxicity. We report a case of amiodarone pulmonary toxicity, who presented with hemoptysis and was successfully treated with the cessation of amiodarone, with review of the relevant literature.

A Case of Diffuse Alveolar Damage Induced by Cyclophosphamide

Approximately 100 drugs have been reported to affect the lungs adversely. Among these, pulmonary toxicity caused by antieneoplastic agent. is being recognized more frequently. Cyclophosphamide is an immunosuppressive alkylating agent used for the treatment of a wide variety of malignant and nonmalignant diseases. The incidence of pulmonary toxicity is probably less than 1 percent The first case was reported in 1967. Since then, more than 20 well-documented cases of pulmonary toxicity associated with cyclophosphamide have been reported in the literature. In Korea, three patients were identified with cyclophosphamide-induced lung disease. The typical features of toxicity include dyspnea, fever, cough, new parenchymal infiltrates, gas exchangs abnormalities on pulmonary function tests, and pleural thickening on chest roentgenogram. The best approach to management is early diagnosis, discontinuation of the offending drug and administration of corticosteroid therapy. Recently, we experienced a case of diffuse alveolar damage induced by cyclophosphamide. The patient presented with early-onset pulmonary toxicity and died of repiratory failure despite early use of corticosteroid.

Pulmonary Toxicity in Patients With Advanced-Stage Germ Cell Tumors Receiving Bleomycin With and Without Granulocyte Colony Stimulating Factor

The purpose of this study is to determine whether co-administration of granulocyte colony stimulating factor (G-CSF) and bleomycin results in enhanced pulmonary toxicity compared with bleomycin alone. A retrospective analysis comparing two groups of patients with advanced germ cell tumors receiving combination chemotherapy that includes bleomycin with or without G-CSF. Indiana University Medical Center. Group A consisted of 29 patients with advanced-stage germ cell tumors who were treated with combination chemotherapy that included bleomycin. All patients received concurrent prophylactic G-CSF. Group B consisted of 57 patients with advanced-stage germ cell tumors who were treated on a phase 3 study comparing standard BEP (bleomycin, etoposide, cisplatin) to BEP with twice the cisplatin dose. None of these patients received growth factor. Of the 29 patients who received concurrent chemotherapy and G-CSF, ten (34%; 95% confidence interval [CI], 17.9 to 54.3%) were believed to have clinically significant bleomycin toxicity. Of the 57 patients who did not receive growth factor, 19 (33%; 95% CI, 21.4 to 47.1%) had bleomycin-related toxicity. There was no difference in the incidence of pulmonary toxicity between the groups (p = 1.00 by Fisher's Exact Test). There is no increase in pulmonary toxicity with co-administration of G-CSF and bleomycin compared to bleomycin alone in patients with advanced germ cell tumors.

Mitomycin-C and metronidazole in the treatment of advanced renal-cell carcinoma.

Fifteen patients with advanced renal-cell carcinoma were treated with the combination of mitomycin-C 14-20 mg/m2 i.v. every 7 weeks and metronidazole 1,500 mg/m2 p.o. 12 and 1 h before and 6 and 24 h after the mitomycin-C. Of 12 patients evaluable for response, three (25%) responded with partial remissions. Myelosuppression did not appear to be increased over that seen with mitomycin-C alone. Pulmonary toxicity occurred in three patients and was fatal in two. The incidence of pulmonary toxicity was probably increased over that seen with mitomycin-C alone. Renal toxicity was also seen. Based on this small study, it was our feeling that this dose-schedule of metronidazole did not appear to result in enough of an augmentation of the efficacy of mitomycin-C against renal-cell carcinoma to justify the incidence of serious toxicity.