bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and tolerability of a weekly schedule of docetaxel-cisplatin as first-line treatment for advanced non-small cell lung cancer (NSCLC)
Authors: Binder D. , Hackenthal M. , Graseck L. , Schweisfurth H. , Schäper C. , Krüll M. , Temmesfeld-Wollbrück B. , Suttorp N. , Beinert T. , Hellriegel K.
Published: March 2020

18159

Background: Docetaxel-cisplatin, administered every 3 weeks, is an effective first-line chemotherapy for locally advanced or metastatic NSCLC. However, this regimen is commonly associated with neutropenia and neutropenic infections. Moreover, the extensive hydration required with cisplatin given every 3 or 4 weeks makes outpatient treatment difficult. We assessed the efficacy and tolerability of weekly docetaxel-cisplatin, which may be better tolerated than the standard regimen. Methods: Patients (pts) with histologically confirmed stage UICC IIIB (malignant effusion) or IV NSCLC were treated with docetaxel (35 mg/m2, 30 min. infusion) and cisplatin (25 mg/m2, 30-min. infusion) on Days 1, 8, and 15, every 4 weeks for 4–6 cycles. Pts received ondansetron 8 mg iv and dexamethasone 8 mg iv preceding every day of chemotherapy and oral dexamethasone 2 x 4 mg daily from the day before until the day after chemotherapy. NK1-antagonists were given at the investigator’s discretion. On each day of therapy, 2750 mL of fluid was infused over 3.5 h. Most pts were treated in an outpatient department. Safety was assessed using CTCAE v3.0. The primary endpoint was response rate (RECIST). Results: 45 pts were enrolled; efficacy and tolerability data were available for 43 pts. 12/45 pts achieved an objective response (11 partial; 1 complete; ITT response rate 27%). Median time to progression was 3.9 months. Pts received a median of 3 full cycles. 4 pts (9%) required dose reductions. No cases of neutropenic fever/infections or grade 2–4 thrombocytopenia were observed. Only 2 pts (5%) had grade 3 neutropenia. One pt (2%) experienced grade 3–4 nausea/vomiting. 5 pts died during therapy for reasons not unequivocally attributable to tumor progression (bacterial meningitis with normal neutrophil counts [n=1], pneumonia with normal neutrophil counts [n=1], pulmonary arterial embolism [n=1], unknown [n=2]). Conclusions: Docetaxel-cisplatin administered weekly was well tolerated. Hematologic toxicity and neutropenic fever were uncommon. Docetaxel-cisplatin can be safely administered with relatively low hydration volumes in an outpatient setting. Survival data will be presented.

No significant financial relationships to disclose.
Phase II study of docetaxel and carboplatin in elderly patients with advanced non-small cell lung cancer: Final results
Authors: Yoshimura N. , Kudoh S. , Kimura T. , Mitsuoka S. , Yana T. , Hirata K.
Published: March 2020

18161

Background: Single-agent chemotherapy has been considered as standard treatment for elderly patients with non-small cell lung cancer (NSCLC). However recent subset analyses suggest that platinum-based combination chemotherapy may be safely administered to the elderly with good performance status (PS). We evaluated the efficacy and safety of carboplatin and docetaxel in a phase II study of elderly patients aged 70 years or older. Methods: Chemotherapy-naive patients aged =70 years with advanced NSCLC (IIIB-IV), ECOG performance status (PS) of 0–2, a measurable lesion, and adequate organ functions were enrolled. Patients received carboplatin (AUC 5) and docetaxel (60 mg/m2) administered on day 1 every 3 weeks. The primary endpoint was response rate (RR). This study, with a planned sample size of 25, had 80% power to support the hypothesis that the true RR was >30%, and 5% significance to deny the hypothesis that the true RR was <10%. Results: Between October 2003 and April 2006, 30 elderly patients with NSCLC were enrolled in the study and all patients were treated. Demographics: M/F 20/10; PS 0/1/2 2/23/5; median age 75 (range 70–84). Median number of treatment cycles was 3.5. Responses in the 30 evaluable patients included 1CR; 13PR; for an objective RR of 46.7% (95% CI 28.8–64.6%). By January 4, 2007, 21 (70.0%) of 30 patients had died. Median follow-up for survival was 8.4 months. The median time to tumor progression was 4.4 months, and the median survival was 9.9 months. The 1-year survival rate was 43.3%.Grade 3/4 hematologic toxicities included leukopenia (80.0%), neutropenia (86.7%), anemia (16.7%) and thrombocytopenia (3.3%). Non-hematologic toxicities were mild with no grade 4 toxicities; grade 3 nausea (10.0%), anorexia (30.0%), diarrhea (13.3%), fatigue (6.7%), allergic reaction (6.7%), pneumonitis (3.3%), febril neutropenia (16.7%) and infection (10.0%) were observed. Conclusions: The combination of carboplatin and docetaxel was safe and promising for the treatment of chemotherapy-naive elderly patients with advanced NSCLC. This regimen warrants further evaluation in a phase III trial.

No significant financial relationships to disclose.
Medical resource utilization (MRU) and costs associated with paclitaxel poliglumex (PPX) compared to gemcitabine (Gem) or vinorelbine (Vin) in non-small cell lung cancer (NSCLC) patients
Authors: Oldham F. B. , Anastassopoulos K. P. , O'Byrne K. , Maxon M. S. , Schaefer C. P.
Published: March 2020

18172

Background: NSCLC accounts for 80% of lung cancer cases and is commonly treated with taxanes. PPX is a phase III, biologically-enhanced, investigational, chemotherapeutic for treatment of NSCLC that links paclitaxel to a biodegradable polyglutamate polymer that potentially spares normal tissue exposure to chemotherapy toxicities. Methods: MRU data were collected as part of a multinational, randomized trial that compared PPX (n=191) to Gem or Vin (n=190) in chemotherapy-naïve advanced NSCLC patients with a performance status of 2. MRU and costs associated with chemotherapy administration and non-protocol-driven care were compared over the study period. Costs (2005 U.S. dollars) were assigned from a U.S. payer perspective. Results: Patient demographics were similar (p>0.05) between groups (mean age: 62 yrs, 72% male, 89% Caucasian). PPX had slightly longer median survival (220 vs. 198; p=0.686) with significantly fewer adverse events (all grades; 2.0 vs. 3.0; p=0.011) and significantly more chemotherapy cycles (3.4 vs. 3.9; p=0.007), per subject. Additionally, PPX had fewer outpatient visits (0.6 vs. 1.7; p<0.001), diagnostic tests (0.6 vs. 1.9; p<0.001), and days on non-chemotherapy medications (64.4 vs. 91.2; p<0.001), per subject. There was no significant difference in number of hospitalizations (0.04 in both groups; p=0.786), length of stay among those hospitalized (8.4 days PPX vs. 6.1 days Gem or Vin; p=0.301), or procedures (0.02 PPX vs. 0.04 Gem or Vin; p=0.238), per subject. Average costs per subject were significantly lower in PPX for outpatient visits ($34 vs. $78; p=0.014), non-chemotherapy medications ($717 vs. $911; p<0.001), and chemotherapy administration ($1,557 vs. $3,601; p<0.001) and similar for inpatient stays ($210 PPX vs. $244 Gen or Vin; p=0.794). Conclusions: This analysis suggests that, in addition to providing a clinical benefit of fewer adverse events, PPX results in reduced MRU and associated costs compared to Gem or Vin in treating NSCLC. These cost savings can be weighed against the cost of PPX and may provide a pharmacoeconomic advantage. Further research is warranted to confirm these results in routine clinical practice.

[Table: see text]
A phase II trial of adjuvant UFT after sequential chemotherapy and radiotherapy in patients with stage IIIB non-small cell lung cancer and non-oriental ethnicity
Authors: Melo A. C. , Lima D. S. , Small I. A. , Olmedo D. B. , Toscano E. , de Biasi P. , Martins R. , Ferreira C. G. , Zukin M.
Published: March 2020

18175

Background: The goals of chemoradiotherapy in non-small cell lung cancer (NSCLC) with stage III disease are to achieve local control, for which radiotherapy plays the main role, and eradicate occult distant metastases by chemotherapy. Systemic progression remains a significant cause of morbidity and mortality in these patients. Japanese trials showed that the combination of uracil and tegafur (UFT) improves survival in patients with early NSCLC. The Brazilian National Cancer Institute (INCA) conducted a phase II trial to evaluate the use of adjuvant UFT in patients with IIIB NSCLC treated with sequential chemoradiation. Methods: The eligibility requirements were stage IIIB NSCLC, an ECOG performance status 0 or 1 and normal end organ function. Patients were treated with induction chemotherapy with cisplatin (100 mg/m2 - days 1 and 29) and vinblastine (5 mg/m2/week for 5 weeks) followed by 60 Gy of thoracic radiotherapy. Two weeks after the end of radiotherapy they started a fixed UFT oral dose (400 mg/day), administered continuously for one year if no progression was detected in this interval. Results: Between May 1999 and October 2003, 22 patients were enrolled; 15 were male (68.2%); 65% were white (no patients had oriental ethnicity); 11 were adenocarcinoma (50%), 9 squamous cell (40.9%); the median age was 55.5 years (range: 45–74 years). UFT’s toxicity was manageable with 13.6% of grades 3 and 4 toxicities (mainly fatigue, diarrhea, nausea and vomiting). Two patients discontinue UFT due to limiting toxicity (1 patient due to diarrhea and 1 due to nausea and fatigue). Median time on UFT was 5 months (range: 0.5–12 months). Median follow-up was 13.5 months (range: 6–77 months) and five patients are still alive. The median overall survival (OS) was 14 months (95% CI: 10.6–17.3) and the median progression-free survival was 8 months (95% CI: 3.4–12.5). Conclusions: UFT in this fixed dose schedule was well tolerated, but our results are almost identical to the Dillman′s original report with sequential chemotherapy and radiotherapy in stage IIIB NSCLC (13.7 months OS). Despite our limited sample size these data may suggest that adjuvant UFT do not add any benefit to sequential chemoradiation in this non-oriental population.

No significant financial relationships to disclose.
A phase I study of amrubicin (AMR) and irinotecan (CPT-11) in relapsed small cell lung cancer
Authors: Mio T. , Kawahara M. , Fukushima M. , Yanagihara K. , Daimon T. , Furuse K.
Published: March 2020

18181

Background: AMR and CPT-11 have shown excellent activity in extensive small cell lung cancer (SCLC). The aim of this study was to determine the maximum tolerated dose (MTD) of amrubicin in combination with a fixed dose of CPT-11. Methods: Eligibility criteria were patients having pathologically proven SCLC, had relapsed after one or two previous chemotherapies, ECOG performance status (PS) of 0–2 and adequate organ function. Irinotecan was delivered as 50 mg/m2 on days 1 and 8, every 21 days. AMR was delivered on day 1. Doses of AMR were level 1: 80mg/ m2, level 2: 90 mg/m2 and level 3: 100 mg/ m2. Dose elevation was determined using continuous reassessment method (CRM). Tolerability was assessed after the 1st cycle. Another two cycles were conducted when disease progression or unacceptable toxicities were not observed. Results: Between June 2004 and October 2006, 18 patients were enrolled with the following characteristics: male/female, 15/3; median age, 66.3 years (range 57–61); PS 0/1/2: 4/14/0. Median number of previous treatment cycles was 5. A total of 40 courses were conducted. Grade 3/4 hematological toxicities of 1st cycle were: leukocytopenia: 67% (G3/4: 8/4); neutropenia: 89% (G3/4: 6/10), thrombocytopenia: 11% (G3/4: 1/1). Grade 3 febrile neutropenia occurred in 1 patient. Other grade 3 or greater non-hematological toxicities were observed in 4 of 40 courses (grade 3 infection in 3 courses and diarrhea in 1). In the first course, DLT was observed in 2 of 6 patients at dose level 2 (prolonged grade 4 neutropenia, febrile neutropenia), in 1 of 6 at dose level 3 (prolonged grade 4 neutropenia), MTD of amrubicin were determined by CRM to be 100 mg/m2 (level 3). Objective response was obtained in 4 patients (28%). Conclusions: This combination was well tolerated and showed activities in SCLC, though hematological toxicities were rather severe. Phase II trials are being planned in chemo naïve SCLC.

No significant financial relationships to disclose.
Asbestos-related malignant mesothelioma in Japan
Authors: Kishimoto T.
Published: March 2020

18182

Large amounts of asbestos use from 1960’s induced the increase of death caused by malignant mesothelioma in Japan. However, a national survey of the relationship between malignant mesothelioma and asbestos exposure, as well as diagnosis and treatment of malignant mesothelioma has not done up to today. One hundred and fifty-three cases of malignant mesothelioma diagnosed and treated in the Rosai Hospitals located all over Japan were studied, and 132 cases (80.4%) proved to be the definite diagnosis of malignant mesothelioma; another 21 cases were diagnosed as lung cancer, etc. As for definite 132 cases, 105 cases are male and other 27 cases are female with the ratio of 3.9:1. Ages ranges from 28 to 92 years old with the mean of 66.2 years old. One hundred and twelve cases originated from pleura, 18 cases from peritoneum, and each one case originated from pericardium and testicular tunica vaginalis. Final diagnosis of 104 cases (78.8%) was done by the tumor tissues. According to IMIG classification, stage I was 29 cases, stage II 6 cases, stage III 28 cases and stage IV was 44 cases. For the treatment, 29 cases were done extrapleurectomy, 58 cases were chemotherapy and other 39 cases were best supportive care. Median survival term of 132 cases were 9.5 months with 9.8 months of pleural origin and 5.6 months of peritoneal origin. By the clinical staging, stage I and II were 17.2 months, stage III 10.4 months and stage IV 5.4 months. By the treatment, extrapleurectomy was 18.1 months, chemotherapy 8.0 months and palliative care was 5.7 months. Seventy six percent cases were induced by occupational asbestos exposure and the mean exposuring time was 27.6 years and the mean latency was 43 years. Occupational histories were mainly shipbuilders, carpenters, electricians and piping workers. Summary: Seventy-six percent of Japanese malignant mesothelioma appeared by the occupational exposure to asbestos. Seventy-eight percent of final diagnosis were done by histological examination of tumor tissue. Extrapleurectomy was effective for the prognosis.

[Table: see text]

No significant financial relationships to disclose.
Second-generation inhibitors of fatty acid synthase for lung cancer treatment
Authors: Orita H. , Coulter J. , Tully E. , Pinn M. , Thupari J. , Pomper M. , Townsend C. , Ettinger D. , Kuhajda F. , Gabrielson E.
Published: March 2020

18185

Fatty acid synthase (FAS) is highly expressed in many human cancers, including lung cancers. Previous work has shown that blocking FAS activity by cerulenin, a natural antibiotic, or C75, a first-generation synthetic small molecule, leads to apoptosis in cells that overexpress this enzyme. However, the use of C75 is limited by the dose-dependent anorexia that appears to be associated with stimulation of fatty acid oxidation. Pharmacokinetics studies show that the activity of C75 peaks within hours of administration and by 24 hours, approximately 80% of activity is lost. Thus, the effectiveness of C75 is limited by this short duration of anti-neoplastic activity and the prolonged anorexic effects.Several second-generation novel FAS-inhibitory compounds have been synthesized that show significant inhibition of FAS, without parallel stimulation of fatty acid oxidation. Among the most promising of the compounds is C93, which inhibits FAS at nearly equal potency as C75, but has significantly less stimulation of fatty acid oxidation. We treated mice with xenografts (orthotopic and subcutaneous) developed from 3 different human lung cancer cell lines (H460, A549, and LX-7) with daily intraperitoneal injections of C93 (5 days/week) at 50 mg/kg for 4 weeks and observed significant (up to 70%) inhibition of tumor growth in all xenograft models tested. Furthermore, no significant weight loss and no organ-specific toxicity were recognized in treated animals. These results suggest that it is possible to pharmacologically uncouple inhibition of FAS from stimulation of fatty acid oxidation, and thus achieve anti-neoplastic activity by inhibition of FAS without significant drug-induced anorexia. Finally, we tested an oral formulation of C93 with the intent of developing a dosing protocol suitable for clinical applications. Similar levels of drug in tumor tissue, and similar inhibition of fatty acid synthase enzyme activity, were seen after oral and intraperitoneal administrations of drug. Furthermore, repeated oral administration of C93 to animals with subcutaneous H460 lung cancer xenografts inhibited tumor growth to a similar level observed after intraperitoneal administration. Thus, fatty acid synthase appears to be a promising target for lung cancer treatment.

No significant financial relationships to disclose.
Difference between skin toxicities in erlotinib (E) and gefitinib (G) in the treatment of advanced non-small cell lung cancer (NSCLC)
Authors: Defferrari C. , Loprevite M. , Brianti A. , Catania G. , Grossi F. , Pronzato P.
Published: March 2020

18187

Background: Cutaneous toxicities due to E or G are common and reversible adverse effects. In the two large randomized trials with E (Shepherd F et al, NEJM 2005) and G (Thatcher N et al, Lancet 2005) skin rash toxicity incidence seems different between the two drugs: all grades (gr) were observed in 76% and 37% of patients (pts), gr 3–4 in 9% and 2% respectively. The aim of this study was to assess the incidence of the most common toxicities occurred in a cohort of pts treated with E or G in the same period of time and evaluated by the same medical staff according to the Common Toxicity Criteria version 3.0. Methods: From May 2005 to July 2006, 47 pts suitable for a treatment with an EGFR inhibitor were evaluated for their eligibility in an open label phase II trial with E 150 mg/day. Pts ineligible for the latter (16) were treated with G 250 mg/day in a compassionate-use program. Fifteen pts were treated with G at progression after E. Results: Toxicities (all gr, gr 3/3–4) for E vs G consisted in: acneiform rash (64 vs 25%, 13 vs 0%), rash/desquamation (83 vs 19%, 12 vs 0%), pruritus (38 vs 16%, 6 vs 0%), dry skin (48 vs 32%, 3 vs 0%), nail changes (15 vs 6%, 3 vs 0%), diarrhea (54 vs 19%). When pts were treated with both E and G the toxicities (all gr, gr 3/3–4) observed were: acneiform rash (93 vs 20%, 27 vs 0%), rash/desquamation (100 vs 20%, 20 vs 0%), pruritus (41 vs 13%, 7 vs 0%), dry skin (54 vs 27%, 7 vs 0%), nail changes (27 vs 7%, 7 vs 0%), diarrhea (53 vs 7%). Conclusions: Our data are not conclusive being a non-randomized trial. However, these results suggest that there are less cutaneous adverse effects with G. This difference may be probably attributed either to the dose or the bioavailability of E.

No significant financial relationships to disclose.
Small cell lung cancer in African Americans
Authors: Eads J. , Fu P. , Patrick L. , Levitan N. , Dowlati A.
Published: March 2020

18194

Background: Several factors associated with prognosis in patients with small cell lung cancer (SCLC) have been established. The association between these known prognostic factors and race, in particular in African Americans has not been reported. This study was conducted to detect differences in presentation and prognostic factors among African Americans when compared to Caucasians. Methods: A retrospective chart review was performed identifying patients diagnosed with SCLC between July 1998 and December 2005. Data collected included demographic information (age, gender and race) as well as clinical information: stage at time of diagnosis, date of diagnosis, date of death, sites of metastases, response to chemotherapy as well as presenting symptoms and lab values including serum sodium, hemoglobin, WBC, platelets, LDH and any evidence of a neurological presentation. Results: Data was available for 198 patients. There was no significant association between race and stage (p=0.594), gender and stage (p=0.731), age and stage (p=0.505) or presence of a neurological symptom at time of diagnosis and stage (p=0.63). There was a trend that African Americans were more likely to present with a neurological symptom when compared to Caucasians (25% vs. 17% respectively) but this was not statistically significant (p=0.285). There was a significant association between race and gender (p=0.019). Of African Americans with SCLC, 71.4% were female while among Caucasians there was a more even distribution between sexes (51% female, 49% male). No significant difference was detected in overall survival when gender or race were examined (p=0.595 and p=0.953 respectively) and the difference when evaluating those with a neurological presentation was marginal (p=0.086). Other prognostic factors were similar amongst Caucasians and African Americans. Conclusions: When compared with Caucasian females, African American females are more likely to be diagnosed with SCLC than their male counterparts. Although not statistically significant, there is also a trend that African Americans with SCLC are more likely to present with neurological symptoms.

No significant financial relationships to disclose.
An association between lung cancer and gastroesophageal reflux
Authors: Ghanem Z. , Sedfawy A. , Debari V. , Maroules M.
Published: March 2020

18195

Background: Many studies have demonstrated the association between gastroesophageal reflux and a wide spectrum of extra-esophageal complications of the upper aerodigestive tract. A major risk factor for adenocarcinoma of the esophagus is intestinal metaplasia, which occurs as a consequence of GERD. In addition to that, laryngoscopy and bronchoscopy can reveal findings with a high positive predictive value for the presence of GERD. The probable role of this chronic irritative disorder as a causative agent in carcinoma of the lung has not been studied. The aim of our study is to determine the correlation between GERD and lung cancer. Methods: A hospital based retrospective age, sex, ethnicity and smoking matched case control study was performed in a tertiary care center. The medical records of 325 patients diagnosed with lung cancer and 325 matched control cases were reviewed between January 2003 and December 2005. We looked at many aspects at the presentation of the disease including right or left sided lung cancer, pathology of the tumor and the presence of other co-morbid conditions. GERD diagnosis was determined either by endoscopy, manometry or clinical diagnosis retrospectively. Results: Among the 325 lung cancer patients 75 (23%) were found to have GERD at the time of diagnosis. On the other hand, only 46 (15%) patients were found in the control group. By using the Fisher Exact Probability Test there was a statistically significant increase in the incidence of GERD among lung cancer patients compared to the control group at the time of diagnosis (p=0.0046, 95% CI = 1.21- 2.73 and Odds Ratio =1.82). Patients with lung cancer were also divided into 5 major categories: Adenocarcinoma (n=110, 34%), Squamous cell carcinoma (n=70, 22%), Small cell carcinoma (n=40, 12%), NSCLCA (n=52, 16%) and Others (e.g. large cell, neuroendocrine...etc) (n=53, 16%). Conclusion: Our analyses suggest an association between GERD and lung cancer. For this reason we may consider GERD as a possible co-promoting factor of lung cancer in some patients.

No significant financial relationships to disclose.
False negative rates of PET scanning in bronchoalveolar lung (BAL) cancer and its implication for diagnosis and staging
Authors: Seidler C. W. , Buttar A. , Harrow B.
Published: March 2020

18196

Background: Positron Emission Tomography (PET) scanning is extensively used for the diagnosis and staging of NSCLC lung cancer. Studies have shown PET scanning has a higher sensitivity and specificity in NSCLC than conventional diagnostic studies. False negative results in bronchoaveolar (BAL) lung cancer have not been systematically studied. We conducted a retrospective review to report and evaluate the low sensitivity of PET scanning in BAL when compared to other types of NSCLC cancer. Methods: We reviewed records of all patients who were diagnosed with lung cancer at Saint Vincent Hospital from 2000 to 2005. A total of 1361 patient were identified with a pathologically confirmed diagnosed of lung cancer out of which PET scanning was done in 36. All of these 36 cases reported NSCLC cancer: 29 NSCLC (adenocarcinoma 8, squamus cell 4, undifferentiated 6, non-small cell carcinoma 10), 7 bronchoalveolar carcinoma (BAL). Results: Among the cases diagnosed with NSCLC lung cancer at our institution, PET scans were done in 36 cases. Adenocarcinoma was found in 8 cases, all of which had positive PET reports. Squamous cell carcinoma was found in 4 cases, non-small cell carcinoma (not otherwise specified) was found in 10 cases, carcinosarcoma was found in 1 case, and undifferentiated carcinoma was found in 6 cases, all of which had positive PET reports and no false negatives (n=29/29,100%). Surprisingly, in the 7 bronchoalveolar cancer cases, only one PET scan was positive with 6 false negative reports (n= 1/7, 14.2%). A bivariate analysis (chi-square with Yate’s correction for continuity) revealed that the PET scan false negatives are significantly higher (p < 0.0000007) for BAL when compared to other types of NSCLC cancers. Conclusions: PET scanning does not appear to be sensitive in the stagging and detection of BAL lung cancer with sensitivity of 14%. Routine use of PET scans for staging and diagnosis of BAL is not supported by this study.

No significant financial relationships to disclose.
Pre-medications of weekly taxanes in advanced non-small cell lung cancer
Authors: Huang X. , Ye Z. , Lin Y.
Published: March 2020

18210

Background: Taxane is a widely accepted treatment in advanced non-small cell lung cancer (NSCLC). However, a standard pre-medication for weekly taxane has not been established at present. We conducted this study to evaluate the efficacy,safety and pre-medication of weekly paclitaxel /docetaxel schedule in the treatment of advanced NSCLC and to obtain an optimal pre-medication protocol for weekly paclitaxel /docetaxel. Methods: From December 2001 to June 2006, 78 patients with advanced NSCLC (Stage III, IV) were recruited from Department of Chemotherapy, Jiangsu Cancer Hospital and Research Institute. Eleven cases were treated with paclitaxel 80–100 mg/m 2 by intravenous infusion(ivi)on days 1 and 8, 23 cases were treated with paclitaxel 50–80 mg/m2 ivi on days 1, 8 and 15, 14 cases were treated with docetaxel 25–35 mg/m2 ivi on days 1,8 and 15,30 cases were treated with docetaxel 35–45 mg/m2 ivi on days 1 and 8, all combined with a platinum(cisplatin, oxaliplatin or carboplatin), followed by 1 week rest. Four pre-medications were attempted. Results: All 78 patients received a total of 202 courses of treatment. Dose limiting toxicity was myelosuppression. Grade 3 and 4 leukopenia occurred in 19.2% (15/78) of patients. Of the 56 eligible patients who completed at least 2 courses, no patient had a complete response, 20 achieved a partial response and 5 patients showed progression. Toxicity profile of pre-medications included: hypersensitivity (1 case), hypopotassemia (8 cases), myasthenia (5 cases), hiccup (1 case), infection (2 cases). No treatment related death occurred in this study. Conclusions: Weekly administration of paclitaxel/docetaxel is a safe and active protocol for Chinese patients with advanced NSCLC. Our recommendations for weekly pre-medication of taxane are: dexamethasone 2.25 mg-7.5 mg orally 12 h and 2 h before, promethazine 25 mg intramuscularly and cimetidine 600 mg ivi 30 min before paclitaxel; oral dexamethasone 4.5 mg-7.5 mg twice daily for three consecutive days (the day before, the day of, and the day after docetaxel), promethazine 25 mg intramuscularly and cimetidine 600 mg ivi 30 min before docetaxel.

No significant financial relationships to disclose.
Consolidation therapy using cyberknife radiosurgery in NSCLC patients with low-volume residual disease upon completion of systemic therapy
Authors: McLaughlin M. P. , Bordoni R. , Whitaker T. , Zolty P. , Andrews M. , Still T. , Vanapalli J. , Haile K.
Published: March 2020

18213

Background: Pts with unresectable IIIB and IV NSCLC with PS 0–1 are usually treated with chemotherapy (CH) ± targeted therapy (TT) with overall survival (OS) improvement. Upon completion, standard of care is observation. Pts eventually progress within 9 to 12 months. If still in good PS, they are treated with salvage CH or TT; otherwise, they receive palliative care. We evaluated 12 patients with PR to initial therapy, found to have small volume residual disease (SVRD) defined as one or two sites to receive “consolidation” local therapy with Cyberknife Radisurgery (CRS). Methods: Since September 2006, 12 pts with NSCLC, stage IIIB unresectable (3) or IV (9), median age 64 (range 61–78), adenocarcinoma (7), squamous cell carcinoma(5), 9 males, all ECOG PS 0–1, were treated with induction CH (carboplatin/paclitaxel ± bevacizumab, cisplatin/gencitabine) with PR. CT/PET imaging showed SVRD. Eight patients had only one site; four had 2. These patients received CRS consolidative therapy to the following areas: lung-9, mediastinal node - 3, adrenal-2, liver-2. CRS dose depended on the disease site. Peripheral lung lesions - 54 Gy in 3 fractions (fx); medistinal lesions - 50 Gy in 4 fx; adrenal - 24 Gy in 3 fx and liver - 16 Gy. in 1 fx. The primary end point was efficacy (response rate, time to progression in or out of the radiosurgical fields, and OS) compared with historical matched controls. The secondary end point was safety and tolerability of CRS. Results: After a median follow up period of 65 days, all evaluable pts are still alive and without clinical or radiological (CT/PET) evidence of disease progression in or outside the sites of CRS. The treatment was well tolerated with no Grade 3–5 complications. PS remained 0–1 in all patients. Conclusions: Patients with advanced NSCLC benefit from systemic therapy with symptoms control and improved QoL and OS. Upon completion of therapy, observation is the current standard or care. Patients with good PS and SVRD tolerated CRS consolidation therapy remarkably well and may benefit with added symptoms control, improved TTP and even OS. At the June meeting efficacy and toxicity data of a projected population of 30+ patients, with a medial follow up of 8 months, will be presented.

No significant financial relationships to disclose.
Absolute lymphocyte count at time of radioimmunotherapy predicted time to progression in patients with relapsed follicular lymphomas
Authors: Porrata L. F. , Ristow K. , Witzig T. E. , Wiseman G. A. , Tuinstra N. , Markovic S. N. , Markovic S. N.
Published: March 2020

18505

Background: Besides radiation, the immunologic mechanisms of action of 90Y ibritumomab tiuxetan (Zevalin) radioimmunotherapy (RIT) have been attributed to complement mediated lysis and antibody-dependent cellular cytotoxicity (ADCC). We hypothesized that a stronger host immune system prior to Zevalin therapy for relapsed follicular (grade 1&2) lymphomas (FL) would result in an improved time to progression (TTP). As a surrogate marker of host immune status, we studied absolute lymphocyte count (ALC) prior to Zevalin therapy and its impact on TTP in relapsed FL patients. Methods: Between 1996 and 2006, 75 patients with relapsed FL were treated with single agent Zevalin (0.4 mCi/kg, maximum of 32 mCi) at the Mayo Clinic. ALC was obtained from the complete blood cell count prior to RIT. Results: The median age of the cohort was 60 years (range, 29–82 years). 36% (27/75) patients were rituximab refractory. The median TTP in all patients was 6.4 months (range, 1–99+ months). Univariately, ALC as a continuous (HR = 0.448, p < 0.006) or dichotomized [ALC = 1.0 x 109/l (HR = 0.684, p < 0.007)] variable was identified as a prognostic factor for TTP. Superior TTP was observed with an ALC = 1.0 x 109/l (N = 32) compared with an ALC < 1.0 x 109/l (N=43) (median: 12.4 months vs 6.5 months, respectively, p < 0.007). Both groups were balanced in regard to the Follicular Lymphoma International Prognostic Index (FLIPI). ALC, as a continuous (HR = 0.507, p < 0.02) or dichotomized [ALC = 1.0 x 109/l (HR = 0.697, p < 0.01)] variable was identified as an independent prognostic factor for TTP in the multivariate analysis when compared with FLIPI. In the ALC = 1.0 x 109/l group, 14/32 (44%) of FL patients achieved a TTP = 12 months compared to only 7/43 (16%) in the ALC < 1.0 x 109/l group, (p < 0.02). Conclusions: This study supports our hypothesis that a higher ALC, as a marker of immune status of the patient, predicts longer TTP following Zevalin therapy in relapsed FL.

No significant financial relationships to disclose.
Characteristics of Hodgkin lymphoma in Hispanics compared to other ethnic groups
Authors: Ofori-Ntow S. , Ciobanu B. , Telfer M. , Jajeh A. , Kovarik P. , Nathan S. , Kouz R. , Griza D. S. , Catchatourian R.
Published: March 2020

18510

Background: There is scant literature on the characteristics of Hodgkin’s disease in Hispanics. We studied the characteristics of this disease in Hispanics compared to other ethnic-racial groups in our large multiethnic Hodgkin’s disease caseload. Methods: A retrospective analysis of all the Hodgkin’s disease cases diagnosed between 2003 and 2006 was undertaken, using Fisher exact test. Results: Of 289 cases of lymphoma diagnosed, 65 (23%) were Hodgkin’s disease compared to SEER data of 11%; Hispanics 40%, African Americans (AA) 41%, Caucasians 19%. Median age at diagnosis: Hispanics 26, AA 27, Caucasians 38. Among the AA: 85% were men 15% women, Hispanics: 58% men 42% women, Caucasians: 33% men, 67% women (p value 0.004). Histological subtypes: Nodular sclerosis 82 % (58): AA 45%, Hispanics 34%, Caucasians 21%; Mixed cellularity 21% (8): Hispanics 75%, AA 12.5%, Caucasians12.5% (p value 0.079). Among Hispanics 62% were clinical stage 1 or 2, 38% stage 3 or 4; Caucasians 75% stage 1 or 2, 25% stage 3 or 4; AA 33% stage 1 or 2 and 66% stage 3 or 4 (p value 0.029). Among the 16 patients with limited stage disease 50% were Hispanics, 25% Caucasians and 25% AA. Of the 49 patients with advanced stage disease, 70% of the Hispanics had IPS Score 0–3, 30% had Score 4–7. Among the AA, 70% had IPS Score 0–3, 30% Score 4–7, while 33% of the Caucasians had IPS Score 0–3, 67% had Score 4–7 (p value 0.077). Conclusions: Mixed cellularity subtype is more common in the Hispanics while the nodular sclerosis subtype is relatively common in African Americans. Hispanics had early clinical and limited stage disease at diagnosis. Among the patients with advance stage disease, Caucasians had a higher IPS Score than the Hispanics. The clinical relevance of these observations remains to be determined with further studies.

No significant financial relationships to disclose.
Treg phenotype in T-cell lymphomas
Authors: Morales D. , Beltran B. E. , Castañeda C. , Carrasco A. , Quiñones P. , Yabar A.
Published: March 2020

18513

Background: Foxp3 is a key regulatory gene required for the development and function of: regulatory CD4+CD25high T cells (Treg) specialized in maintaining the balance between immunity and tolerance and activated conventional CD4+CD25low T cells without suppressive activity. Previous studies had reported the origin of Adult T-cell Leukemia/Lymphoma cells (ATLL) in Foxp3 T cells and in other lymphomas types the FOXP3 expression was only detected in the reactive T-cell background. Our objetive was to determine the presence of Treg phenotype cells by the FOXP3 expression in T-cell lymphomas. Methods: A retrospective study was performed on 48 samples collected from diverse T-cell lymphomas in our institution. A highly sensitive immunohistochemical method was used to demonstrate Treg phenotype by FOXP3 protein expression with a mouse monoclonal antibody (clone 236A/E7ABCAM) in most formalin-fixed paraffin-embedded tissue sections from lymph nodes, skin, bone marrow and extranodal sites samples as cavum and stomach. We did not co-stained with CD25 and considered a FOXP3+ tissue when positivity was > 20% of tumor cells. The statistical method was descriptive and survival was calculated using the Kaplan-Meier method. Results: Among the 48 evaluable T-cell lymphomas collected, 33 were ATLL, 8 unspecified peripheral T-cell lymphomas (U-PTCL), 6 mycosis fungoides (MF) and 1 cutaneous aggressive epidermotropic CD8(+) cytotoxic T-cell lymphoma. Among the 33 ATLL: lymphomatous=17, acute=11, smoldering=1, chronic=1, cutaneous=1 and undefined=2. FOXP3 expression in tumour cells was detected in 24% (8/33) of ATLL cases and in 37% (3/8) of U-PTCL. It was negative in MF tumour cells and aggressive epidermotropic CD8(+) cytotoxic T-cell lymphoma Among the ATLL cases FOXP3 positivity were obtained in 35% (6/17) of lymphomatous type; 18% (2/11) of acute ones and none in others ATLL types studied. Interestingly 3 U-PTCL had Treg phenotype and were related to EBV (LMP1 positive); two had extranodal primary ( parotide and cavum) and one was nodal. We failed to demonstrate any correlation between FOXP3 status and survival. Conclusions: Some ATLL and U-PTCL had Treg phenotype. In our work Foxp3 expression was not found to be a prognostic factor.

No significant financial relationships to disclose.
Phase 2 study of suberoylanilide hydroxamic acid (SAHA) in relapsed or refractory indolent non-Hodgkin lymphoma: A California Cancer Consortium study
Authors: Kirschbaum M. , Zain J. , Popplewell L. , Pullarkat V. , Obadike N. , Frankel P. , Zwiebel J. , Forman S. , Newman E. , Gandara D.
Published: March 2020

18515

Background: The indolent (follicular, marginal zone and mantle cell) lymphomas tend to recur with decreasing intervals of remission post standard chemotherapy. Vorinostat (SAHA, Zolinza), an orally administered hydroxamic acid histone deacetylase inhibitor with activity against class I and II deactylases, with preclinical and clinical activity against various forms of lymphoma, is being studied in patients with relapsed or refractory indolent lymphoma. Methods: Patients with relapsed or refractory follicular, marginal zone, or mantle cell lymphoma are eligible. Vorinostat is dosed at 200 mg po twice daily for 14 consecutive days on a 21 day cycle. CT scanning and marrow biopsy is performed after every three cycles. Patients may have received up to four prior chemotherapy regimens including Zevalin or Bexxar; previous transplant is allowed. Results: 15 patients (9 female, 6 male) have been enrolled thus far. Median age is 64 (40- 78) years One patient was found to have coexisting DLBCL and was removed from study. Four patients were taken off study due to progression, three stopped due to toxicity (fatigue in a 73 yo woman who had stable to improved marginal zone lymphoma after 10 cycles, fatigue and atrial fibrillation in a 65 yo man after 7 cycles, diarrhea in a 78 year old woman after 2 cycles). Complete Response (CR) in a patient with follicular lymphoma was attained after 9 cycles, this CR persists now for eight months at the time of abstract submission off therapy. A partial response (PR) was seen in a 40 yo man with lymphoma progression despite multiple rounds of therapy, with rapidly expanding masses just prior to starting vorinostat, the largest of which was 16x12.3 cm. This lesion currently measures 7.2x4.6 cm, with disappearance of many other sites; patient continues on vorinostat. Three of the patients with continued stable disease beyond 9 cycles have marginal zone lymphoma, while the two responders (CR or PR) have follicular lymphoma. A patient with PET resolution and decreases in two of the involved sites stopping after 10 cycles due to fatigue, developed rapid progression three months after stopping vorinostat. Conclusions: Vorinostat demonstrates preliminary activity against follicular and marginal zone lymphoma.

No significant financial relationships to disclose.
A large multicentric study of gemcitabine-based regimen in relapsed or refractory Hodgkin lymphoma (HL) patients (pts)
Authors: Validire P. , Fermé C. , Brice P. , Diviné M. , Gabarre J. , Bouabdallah K. , Fitoussi O. , Chaoui D. , Soussain C. , Carde P. , Decaudin D.
Published: March 2020

18518

Background: The aim of this study was to assess the efficacy and safety of gemcitabine-based regimen in heavily pretreated HL pts. Methods: Relapsed or refractory HL pts treated with gemcitabine were retrospectively reviewed. Gemcitabine was used as a single agent or administered in combination with vinorelbine, oxaliplatine, doxorubicine, vinblastine, rituximab, and/or corticosteroids. Results: Fifty-five pts treated in 9 departments of clinical hematology between January 1999 and August 2006 were included in the study. Initial characteristics before gemcitabine administration were: nodular sclerosis in 84%; sex ratio M/F 1.1; median age 29 years (range: 15–85 years); advanced stage 84%; extranodal sites were lung, bone, liver, soft tissues, and bone marrow in 68%, 31%, 13%, 21%, and 4%, respectively; Hasenclever index lower than 3 in 20/43 cases (47%). At the end of the first front-line therapy (chemotherapy ± radiotherapy), 19 pts (35%) were in complete response (CR) in whom 13 relapsed within one year, 5 were in partial response (PR), and 31 pts were primary refractory (56%). Median number of previous chemotherapeutic regimen was 3 (range 1–8), 39 pts (71%) have received radiotherapy (RT), and 34 pts (62%) one or two autologous/allogenic stem cell transplantations (A/ASCT). Twenty-nine pts received gemcitabine alone with a median initial dose per injection of 750 mg/m2 (range: 180–1250 mg/m2); Gemcitabine was administered at an initial dose per injection of 1000 mg/m2 (range: 500–1250) in combination with vinorelbine in 10 pts, oxaliplatine in 13 pts in whom 4 with rituximab, and with others drugs in 3 pts. In both cases, the median number of combined gemcitabine regimen injections was 6 (range: 1–27). Toxicity was mainly hematological (75% of pts developed bi- or pancytopenia) or infectious (13%). Among all included pts, 6 were in CR (11%) and 5 in PR with an overall response rate of 20%. Among the 6 CR, 5 pts received thereafter A/ASCT and 2 pts RT, with 2 persistent CR at 16 and 44 months. In univariate analysis, none prognostic factor for response to gemcitabine was identified. Conclusions: This study, which constitutes one of the most important series, showed a mild efficacy of gemcitabine-based regimen in heavily pretreated HL patients.

No significant financial relationships to disclose.
Absence of chlamydial infection in Japanese patients with orbital adnexal MALT lymphoma
Authors: Yakushijin Y. , Kodama T. , Tanimoto K. , Yamanouchi J. , Azuma T. , Narumi H. , Hato T. , Hasegawa H. , Yasukawa M.
Published: March 2020

18523

Background: The extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a distinct B-cell lymphoma that develops in extranodal sites and usually has an indolent clinical course as a localized disease. Recent clinicopathological studies suggest a strong relation between MALT lymphoma and inflammatory diseases of the epithelium such as autoimmune diseases and infections (Sjogren’s syndrome, Hashimoto’s thyroiditis, Helicobacter pylori infection, and etc.), because chronic antigen stimulation has been causally linked to the development of B-cells lymphoproliferative diseases. MALT lymphoma grows in extranodal lymphoid tissue and exists in epithelium tissues, and it is often difficult to distinguish malignant lymphoid tissue from benign inflammation. This is one cause since recent positive or negative correlations between ocular adnexal MALT lymphomas and chlamydial infections have been reported from different researchers, indicate several possible explanations. Methods: Twenty-three cases of ocular adnexal MALT lymphoma in southern regions of Japan, whose monoclonality was confirmed by immunoglobulin heavy chain gene rearrangement and/or cell surface antigens, were analyzed for evidence of several causative factors using ELISA analysis to detect antibodies and Southern blot analysis followed by specific PCR gene amplification. Results: Our series of patients did not show any serological relations to Epstein-Barr virus, Hepatitis C virus, and Chlamydophila psittaci. Two cases had positive serum antibodies for autoimmunity, and another two cases had positive antibodies against Chlamydia trachomatis. None of our cases showed the presence of chlamydial 16S rRNA and 16S-23S spacer rRNA genes (C. psittac, C trachomatis, C. pneumoniae, and C. felis) after Southern blot analysis followed by PCR amplification. Conclusions: Inflammatory agents are still unknown in our series of orbital adnexal MALT lymphomas, and some types of chlamydial infections are not associated with orbital adnexal MALT lymphoma in southern regions of Japan.

No significant financial relationships to disclose.
Restrospective analysis of non-Hodgkin lymphoma (NHL) patients (p) treated with 90Y ibritumomab tiuxetan (90Y- IT): Iberia RIT database
Authors: Giraldo P. , Gómez Codina J. , Provencio M. , Hernando T. , Tisaire J. L.
Published: March 2020

18526

Background: 90Y-IT is approved for the treatment of refractory NHL. The aim of this study was to collect data of NHL p treated with 90Y-IT within the clinical practice setting, to retrospectively analyze treatment effectiveness and tolerability, in order to provide a pragmatic approach to experimental data. Methods: Multicenter, retrospective study. NHL p treated during last year with 90Y-IT, were registered. Effectiveness endpoints retrospectively studied were: objective response rate (ORR), time to progression (TTP) and overall survival (OS). Clinical prognostic factors were collected to asses their possible influence upon treatment effectiveness, by multivariate analyses. Results: 65 p were registered: M/F, 58.5%/41.5%; median age, 59 years (22–83); ECOG 0–1, 73.3%. Median time since lymphoma diagnosis was 3.6 years. At diagnosis, 84.6% had follicular lymphoma (grade 1, 44.9%; grade 2, 40.8%) and 15.4% non- follicular lymphoma. Most of the cases were refractory to previous treatments (78.1%). Median number of previous treatments was 3 (range 1–8) Median administered dose of 90Y-IT was 0.4 mCi/Kg. ORR was 70.8% (95% CI: 59.8, 81.9). With a median follow-up time of 6 months, median TTP was 16.1 months (95% CI: 11.2, 21.1) and median OS has not been achieved. Within the group of follicular lymphoma, ORR was 74.6% (95% CI: 63.1–86.1) and TTP 17.7 months (95% CI: 14.3, 21.1). Bone marrow involvement and high FLIPI score were significantly associated with higher risk of progression disease: hazard ratio 3.71 (95% CI: 1.00, 13.68) and 21.12 (95% CI: 2.37, 187.91), respectively. Median time to G3–4 haematological toxicity ranged between 27–38.5 days, being the most frequent thrombocitopenia (46.2%) and neutropenia (33.8%). 17 p required red blood cell transfusions (median, 4 U) and 19 required platelet transfusions (median, 7 U). The most frequent G3–4 non haematological toxicity was asthenia (10.8%). Updated survival data will be presented at the meeting. Conclusions: These results obtained with 90Y-IT for NHL treatment within the clinical practice setting are concordant with published experimental data, despite the limitations of the retrospective design.

[Table: see text]