Median Chemotherapy-free Interval Research Articles

Efficacy and safety of lurbinectedin in elderly patients with relapsed SCLC.

8591 Background: Relapsed SCLC is a difficult-to-treat disease. A considerable number of SCLC patients are elderly with associated fragility and numerous comorbidities. Accelerated approval from the US FDA of lurbinectedin (Zepzelca) 3.2 mg/m2 q3wk as second-line therapy in metastatic small cell lung cancer (SCLC) was based on results from a phase 2 basket trial (NCT02454972) showing overall response rate of 35.2% and duration of response of 5.3 months. The ATLANTIS trial (NCT02566993) assessed the combination of lurbinectedin 2mg/m2/ doxorubicin (DOX) 40 mg/m2 as second-line treatment for SCLC vs. a control arm of topotecan/CAV. Methods: This post hoc analysis explores the efficacy and safety of lurbinectedin in relapsed SCLC patients ≥65 years included in both phase 2 basket (26 patients treated with lurbinectedin) and ATLANTIS (121 patients treated with lurbinectedin/DOX and 118 patients treated in the control arm) trials. This analysis did not include patients from the phase 2 basket trial with chemotherapy-free interval (CTFI) < 30 days, as these patients were excluded in the ATLANTIS trial. Results: Median age was similar (72.5 in lurbinectedin basket vs. 69 in ATLANTIS lurbinectedin/DOX vs. 69 in ATLANTIS control arm), most were males (65.4% vs. 57.9% vs. 60.2%), with ECOG PS 1 (65.4% vs. 68.6% vs. 68.6%) and CNS involvement (7.7% vs. 10.7% vs. 15.3%). Median CTFI (days) was also similar (105.5 vs. 123 vs. 120). Median number of cycles was 4 vs. 6 vs. 4. Main efficacy and safety results are shown in the table. Treatment-related adverse events (AEs) were reported in 92.3%, 92.6% and 94.1% of patients, respectively (grade ≥3 in 50.0%, 59.5% and 81.4%). Conclusions: In elderly patients, lurbinectedin seems to be superior to the standard of care in terms of both efficacy (higher response rate and longer duration of response and overall survival) and safety (less associated hematological AEs), which reinforces its role as a treatment option in relapsed SCLC patients ≥65 years. Clinical trial information: NCT02454972 , NCT02566993 . [Table: see text]

Clinical application of radiotherapy in patients with oligometastatic ovarian cancer: a sharp tool to prolong the interval of systemic treatment

BackgroundWith the advances of radiation technology, treatment of oligometastatic disease, with limited metastatic burden, have more chances to achieve long-term local control. Here we aim to evaluate the efficacy and safety of radiotherapy (RT) in oligometastatic ovarian cancer patients.MethodsA retrospective analysis collecting 142 patients (189 lesions) with oligometastatic ovarian cancer were included in the study. All pateints received radiotherapy and the curative effect and response rate were evaluated by diagnostic imaging after 1–3 months of radiotherapy with RECIST. Endpoints were the rate of complete response (CR), chemotherapy-free interval (CFI), local control (LC) rate and overall survival (OS) rate. Toxicity was evaluated by the Radiation Therapy Oncology Group (RTOG). Logistic and Cox regression were used for the uni- and multivariate analysis of factors influencing survival outcomes.ResultsFrom 2013.1.1 to 2020.12.30, a total of 142 ovarian cancer patients (189 oligometastasis lesions) were included in the analysis. Prescribed doses to an average GTV of 3.10 cm were 1.8–8 Gy/fraction, median BED (28–115, a/b = 10 Gy), 5–28 fractions. For 179 evaluable lesions, the cases of CR, partial response (PR), stable disease (SD) and progressive disease (PD) after radiotherapy were 22,39,38 and 80 respectively. The disease control rate (DCR): CR + PR + SD was 55.31%, and the objective response rate (ORR): CR + PR was 34.08%. No patient developed grade 3 or higher side effect. The median CFI was 14 months (1–99 months), and the LC rate was 69.7%, 54.3% and 40.9% in 1 year, 2 years and 5 years respectively. GTV < 3 cm before treatment, platinum sensitivity, time from the last treatment ≥ 6 months, single lesion and BED(a/b = 10 Gy) ≥ 60 are the factors of good LC (p < 0.05). The total OS of 1 year, 2 years and 5 years were 67.1%, 52.6% and 30.3%, respectively. Single lesion (HR 0.598, 95%CI 0.405–0.884), DCR (HR 0.640, 95% CI 0.448–0.918) and ORR(HR 0.466, 95% CI 0.308–0.707) were the significant factors influencing 5-year OS.ConclusionFor patients with oligometastatic ovarian cancer, radiotherapy has high LC, long chemotherapy-free interval, and survival benefits. Subgroup analysis shows that patients with single lesion and good local treatment results have higher overall survival rate, suggesting that active treatment is also beneficial for oligometastatic ovarian cancer patients.

What predicts the clinical benefits of PARP inhibitors in platinum-sensitive recurrent ovarian cancer: A real-world single-center retrospective cohort study from China.

ObjectiveThis study assessed the real-world application, effectiveness, and safety of olaparib and niraparib as maintenance therapies in patients with platinum-sensitive recurrent ovarian cancer (PSROC) in China and investigated clinical factors associated with prolonged benefits of poly ADP-ribose polymerase (PARP) inhibitors to help guide clinician treatment-decision making in daily practice.MethodsThis real-world single-center retrospective cohort study was conducted at the Shandong Cancer Hospital and Institute. Archival data of consecutive patients diagnosed with PSROC who achieved a complete response (CR) or partial response (PR) after the last platinum-based chemotherapy and treated with olaparib or niraparib as maintenance therapy from August 2018 to September 2021 were collected.ResultsOverall, 106 women were included in the cohort. Seventy-two (68%) patients were treated with olaparib, while 34 (32%) received niraparib; 99.1% of the patients were diagnosed with high-grade serous carcinoma, and 73.6% had FIGO stages III–IV. Approximately 71.7% of the patients had received PARP inhibitors after the second platinum-based line and 44.3% of the patients achieved a CR in their last platinum-based therapy. The median platinum-free interval (PFI) after the penultimate platinum-based therapy was 10 (95% CI: 10–13.6) months. The median PFS was 21 (95% CI: 13–24.5) months and the median CFI was 22 (95% CI: 16–26.5) months. Consistent with the univariate analysis, the multivariate analysis identified three independent factors associated with prolonged progression-free survival (PFS) and chemotherapy-free interval (CFI): breast cancer susceptibility gene (BRCA) mutant type (p = 0.005 and p = 0.003); PFI ≥12 months (p = 0.01 and p = 0.006); and CR to last platinum-based therapy (p = 0.016 and p = 0.019). It was found that there was no appreciable difference in any grade 3–4 hematological AE between patients who received olaparib and niraparib.ConclusionMaintenance treatment with olaparib and niraparib is effective and well tolerated for PSROC patients in real-world clinical practice. Three clinical factors were identified that predicted prolonged survival under maintenance therapy with PARP inhibitors: BRCA mutant type, PFI ≥12 months, and CR to last platinum-based therapy. These findings should be further confirmed with an appropriately powered analysis in studies with larger sample sizes.

Surgery in platinum-resistant recurrent epithelial ovarian carcinoma.

BACKGROUNDOvarian cancer is one of the three most common malignant tumors of the female reproductive tract and ranks first in terms of mortality among gynecological tumors. Epithelial ovarian carcinoma (EOC) is the most common ovarian malignancy, accounting for 90% of all primary ovarian tumors. The clinical value of cytoreductive surgery in patients with platinum-resistant recurrent EOC remains largely unclear.AIMTo evaluate the feasibility of secondary cytoreductive surgery for treating platinum-resistant recurrent EOC.METHODSThis was a retrospective study of the clinical data of patients with platinum-resistant EOC admitted to the Cancer Hospital of the University of Chinese Academy of Sciences between September 2012 and June 2018. Patient baseline data were obtained from clinical records. Routine follow-up of disease progression was performed as follows. CA125 assessment and physical examination were performed every 3 wk during treatment, including gynecological examination. Imaging assessment was carried out every 12 wk by B-mode ultrasound, computed tomography, or magnetic resonance imaging. The primary outcome was progression-free survival (PFS). Secondary outcomes included overall survival (OS), chemotherapy-free interval (CFI), and complications. Follow-up ended on April 15, 2019.RESULTSA total of 38 patients were included. R0 resection was achieved in 25 (65.8%) patients and R1/2 in 13 (34.2%). Twenty-five (65.8%) patients required organ resection. Nine (23.7%) patients had operative complications, 36 (94.7%) received chemotherapy, and five (13.2%) had targeted therapy. Median PFS and OS were 10 (95%CI: 8.27-11.73) months and 28 (95%CI: 12.75-43.25) months, respectively; median CFI was 9 (95%CI: 8.06-9.94) months. R0 resection and postoperative chemotherapy significantly prolonged PFS and OS (all P < 0.05), and R0 resection also significantly prolonged CFI (P < 0.05). Grade ≥ 3 complications were observed, including rectovaginal fistula (n = 1), intestinal and urinary fistulas (n = 1), and renal failure-associated death (n = 1). Except for the patient who died after surgery, all other patients with complications were successfully managed. Two patients developed intestinal obstruction and showed improvement after conservative treatment.CONCLUSIONSecondary cytoreductive surgery is feasible for treating platinum-resistant recurrent EOC. These findings provide important references for the selection of clinical therapeutic regimens.

Radiation therapy for vaginal and perirectal lesions in recurrent ovarian cancer

<h3>Objectives:</h3> The role for radiation therapy (RT) to treat ovarian cancer (OC) patients with locally recurrent vaginal/perirectal lesions remains unclear, though we hypothesize that these patients may be salvaged locally and gain long-term survival benefit. We aimed to describe our institutional outcomes using vaginal brachytherapy±intensity modulated radiation therapy (IMRT) to treat this population and report our in-field control rate, RT-related toxicities, post-RT chemotherapy-free interval (CFI), RT-related toxicities, progression-free survival (PFS), and overall survival (OS). We also studied the prognostic impact of platinum status immediately prior to RT. <h3>Methods:</h3> This is a single institution retrospective case series of 17 recurrent OC patients treated with brachytherapy±IMRT for vaginal and/or perirectal recurrences between January 2006 and November 2019. Intent of RT (palliative or definitive) was determined collaboratively by the treating gynecologic and radiation oncologists. PFS and OS were defined from date of RT completion to either progression or death/last follow-up, respectively. <h3>Results:</h3> This was a heavily pre-treated cohort (median 3 prior lines of chemotherapy, range 1-9), with a median follow-up of 28.4 months (range 4.5-166.4) after RT completion (Figure 1). Most patients had high-grade serous histology (9 of 17) with the remainder of patients even distributed between low-grade serous, clear cell, mixed, and carcinosarcoma. Eleven patients were treated with definitive intent, including 4 with isolated vaginal/perirectal disease. Three patients received concurrent chemotherapy or immunotherapy and RT. Four (23.5%) patients had in-field failures at 2.3, 10.9, 23.2, and 25.7 months post-RT, all of whom had been treated with definitive intent. The 9 patients who were platinum-sensitive prior to RT had similar median PFS (8.1 vs. 10.4 months, log-rank p=0.91), but longer OS (53.9 vs 16.5 months, log-rank p=0.03) compared to their platinum-resistant counterparts. Excluding patients with low-grade histology or who were treated with palliative RT, the median CFI was 12.6 months (range 1.3-31.7). When including all patients, the two patients with the longest CFI post-RT included a <i>BRCA2</i> mutation carrier with an isolated vaginal recurrence and a patient with a <i>MLH1</i> somatic mutation treated with concurrent RT and pembrolizumab. RT was well tolerated with 2 (12%) experiencing grade 3/4 gastrointestinal/genitourinary toxicities. <h3>Conclusions:</h3> RT to treat locally recurrent vaginal and perirectal lesions in heavily pre-treated OC patients is safe and may effectively provide locoregional control.

Analysis of the Chemotherapy-Free Interval following Image-Guided Ablation in Sarcoma Patients.

One way to enhance quality of life for patients with metastatic sarcoma is to maximize time off chemotherapy—a chemotherapy-free interval. While image-guided ablation of sarcoma metastases may reduce the need for chemotherapy, it remains unknown how long ablation could extend the chemotherapy-free interval. The purpose of our study was to determine the chemotherapy-free interval in comparison to overall survival and progression-free survival in sarcoma patients who undergo ablation procedures. An IRB-approved, single institution, HIPAA compliant database was queried for sarcoma patients who underwent image-guided ablation procedures between 2007 and 2018. Patient demographics, histologic subtype, and other clinical characteristics were recorded. Kaplan-Meier analysis was performed to compute median overall survival, median progression-free survival (local and distant), and the median chemotherapy-free interval (systemic and cytotoxic) after ablation. Univariate and multivariate analyses were performed using the log-rank test and Cox proportional-hazards model, respectively. A total of 100 sarcoma patients were included in the analysis. The most common histologic subtype was leiomyosarcoma (38%). Median overall survival after ablation of sarcoma metastases was 52.4 months (95% CI: 46.9–64.0 months). The median systemic chemotherapy-free interval following ablation of sarcoma metastases was 14.7 months (95% CI: 8.6–34.3 months). The median cytotoxic chemotherapy-free interval following ablation of sarcoma metastases was 81.3 months (95% CI: 34.3-median not reached). In conclusion, ablation of sarcoma metastases can provide an extended systemic chemotherapy-free interval of greater than 1 year. Ablation of sarcoma metastases may improve patient quality of life by extending the chemotherapy-free interval.

Efficacy and safety profile of lurbinectedin in second-line SCLC patients: Results from a phase II single-agent trial.

8506 Background: Lurbinectedin (L) is a novel anticancer drug that inhibits activated transcription and induces DNA double-strand breaks, leading to apoptosis. Methods: A multicenter phase 2 basket trial assessed the efficacy and safety of L in several cancer types, including small cell lung cancer (SCLC). Primary endpoint was confirmed overall response rate (ORR) by RECIST v.1.1. In the SCLC cohort, a target ORR ≥30% was set. One-hundred and five patients (pts) with ECOG PS 0-2 who had received one prior chemotherapy line were treated with L 3.2 mg/m2 as a 1-hour i.v. infusion on Day 1 q3wk. Results: Median age was 60 years (range, 40-83), 60% were male, ECOG PS 0/1/2 (32%/62%/6%), liver metastasis 41%, history of CNS involvement 3.8%, prior platinum 100%, median chemotherapy-free interval (CTFI): 3.5 (0-16.1) months; prior immunotherapy (IO): 7.6%. Pts received a median of 4 cycles (range, 1-24). Conclusions: L monotherapy is active in second-line SCLC in both resistant and sensitive disease. The acceptable and manageable safety profile is also associated to a convenient treatment administration (Day 1 q3wk). L as second-line treatment in SCLC emerges as a new promising drug for this unmet clinical need. Clinical trial information: NCT02454972. [Table: see text]

The impact of complete chemotherapy stop on the overall survival of patients with advanced colorectal cancer in first-line setting: A meta-analysis of randomized trials

Background. The impact of the duration of chemotherapy on the overall survival of patients with metastatic colorectal cancer (mCRC) is controversial and studies have failed to define a clear standard.Methods. We searched medical literature databases and oncology conferences proceedings for randomized controlled trials (RCT) that compared the overall survival of mCRC patients who received continuous first-line chemotherapy until disease progression versus those who were offered complete treatment stop after a fixed number of cycles. Studies including targeted agents were also included. A meta-analysis of reported hazard ratios (HRs) for survival was performed.Results. We retrieved 240 trials, of which six were eligible and five were included in the pooled analysis of overall survival (N = 3061). The overall survival between continuously delivered chemotherapy and complete stop was not statistically different (HR = 0.93, 95% CI 0.85–1.02; p = 0.12; I² = 5%). The results are similar when we analyzed separately the trials performing randomization before versus after induction therapy. The median chemotherapy free interval in the complete stop group was 3.9 months (3.6–4.3 months). Chemotherapy administered until progression was associated with more adverse effects and impaired quality of life.Conclusion. Compared with first-line continuous chemotherapy administered until disease progression, complete treatment stop did not have a detrimental impact on the overall survival of patients with mCRC. Identification of predictive biomarkers could help clinicians to select the patients who would benefit from continuous cancer-directed therapies.

528PD - The Effect of Chemotherapy Holiday on the Overall Survival of Patients with Advanced Colorectal Cancer: A Meta-Analysis of Randomized Trials

ABSTRACT Background The impact of the duration of chemotherapy on the outcomes of patients with advanced colorectal cancer is controversial. Our objective was to perform a systematic review and meta-analysis of randomized controlled trials (RCT) that compared chemotherapy continuously administered until disease progression versus chemotherapy interruption in patients with metastatic colorectal cancer. Methods We systematically searched for all RCT in which metastatic colorectal cancer patients were randomized to continuous therapy until progression or chemotherapy discontinuation after maximal response or fixed number of cycles. Trials were located through searches of PubMed, Cochrane Library and of ASCO/ESMO abstracts up to February 2012. Two authors independently extracted the data, and consensus was achieved when there was disagreement. Meta-analyses were performed using random-effects model. Hazard ratios (HR) were used for the meta-analysis and were expressed with 95% confidence intervals (CI). Statistical heterogeneity of data was evaluated with the chi-square test, and expressed using the I2 index. Results Our search retrieved 42 RCT, of which five were eligible, with 1815 patients included. The analysis of progression-free survival (PFS) was not possible due to the different definitions of PFS across trials. The median chemotherapy free interval in the discontinuation group was 3.9 months. The pooled analysis of overall survival included 1776 patients (one trial was not included because it did not present extractable data). The metanalysis showed a statistically significant survival benefit with continuously given chemotherapy (HR = 0.90, 95% CI = 0.82 to 0.99; p = 0.03; I2 0%) in comparison to chemotherapy holiday strategy. Quality of life was reported in one trial and no difference was found in it. Conclusions Chemotherapy delivered continuously until tumor progression appears to be associated with a modest but significantly better survival in patients with advanced colorectal cancer over chemotherapy interruption. Continued therapy may be available for selected patients with more aggressive disease. Disclosure All authors have declared no conflicts of interest.

Alemtuzumab maintenance may safely prolong chemotherapy-free intervals in chronic lymphocytic leukemia

This prospective, single-arm study utilized alemtuzumab as a single agent in a novel maintenance schedule in previously treated chronic lymphocytic leukemia patients with the goal of delaying progression of disease and requirement for chemotherapy. In previously treated CLL patients who had achieved stable disease or better, the following schedule of subcutaneous alemtuzumab was administered: a dose escalation in the first week (3, 10 and 30 mg), followed by 7 weeks of 30 mg alemtuzumab once weekly, 16 weeks of 30 mg once every 2 weeks, followed by once every 3 weeks for 24 weeks. Thus, the entire duration of the planned treatment was 48 weeks. A total of 12 patients were enrolled 11 of which had at least one marker of poor prognosis (unmutated, Zap 70+, CD38+, del11q and del17p). The median chemotherapy-free interval was 13 months, and the median time to disease progression was 10 months. Three patients achieved a CR, one achieved nPR, one had a PR, five failed and two had shown a beneficial response but because of recurrent ITP had to stop alemtuzumab. In six of the 10 patients with previously relapsed disease, the chemotherapy-free interval was longer than their prior chemotherapy-free period. One patient had a reactivation of CMV antigenemia, and another had a bacterial pneumonia. There were no grade 3 or 4 toxicities. Alemtuzumab used in a maintenance schedule is a potentially safe and useful tool in delaying disease progression and chemotherapy-free intervals in previously treated CLL patients.

Oxaliplatin/5fluorouracil-based chemotherapy was active and well tolerated in heavily pretreated patients with ovarian carcinoma

The prognosis of patients with platinum refractory disease is dismal. We present data from heavily pretreated patients to whom the folinic acid, 5-fluorouracil and oxaliplatin (Folfox) regimen was administered. The objectives were to assess response rate and to evaluate the safety profile. Patients with recurrent, resistant or refractory pretreated ovarian carcinoma were eligible for oxaliplatin (85 mg/m(2)) and leucovorin (200 mg/m(2)), both given as a 2-h infusion on day 1, followed by a 48-h infusion of 5FU 2,600 mg/m(2) every 2 weeks. Fourteen patients were treated. Median age: 56 years (49-70). Median number of previous chemotherapy regimens: 5 (3-10) and previous platinum-based regimens: 2 (1-3). Median chemotherapy-free interval (interval since the completion of the last-line chemotherapy before the administration of the Folfox regimen): 9.5 weeks (1-39). Median number of administered cycles of Folfox/patient: 8 (2-11 cycles). Two (14.5%) patients had a disease complete response, 2 (14.5%)-partial response, 4 (29%)-stable disease and 6 (43%)-progressive disease. Four (29%) patients had a CA-125 complete response, 2 (14.5%)-CA-125 partial response, 5 (35.5%)-stable CA-125 levels and 3 (21%)-progressive CA-125 levels. There were no grade 4 adverse events or deaths due to the treatment. No dose modifications were required due to toxicity. Folfox seems to be a valuable option for heavily pre-treated patients with ovarian cancer, with an overall response rate, according to RECIST criteria, of 29% and disease stabilization in an additional 29% of patients, with a manageable toxicity profile. These results support further assessment of Folfox as salvage treatment for patients with carcinoma of the ovary or fallopian tube.

Oxaliplatin and 5-fluorouracil in heavily pretreated patients with ovarian carcinoma: A well tolerated and efficient treatment

16028 Background: Recurrent ovarian cancer is an incurable disease. The prognosis of patients with platinum refractory disease is dismal. We present data from heavily pretreated patients with recurrent ovarian cancer to whom the Folfox regimen was administered. Methods: Patients with recurrent, resistant or refractory, pretreated ovarian carcinoma were eligible for this compassionate use program of oxaliplatin (85 mg/m2 in 2 hours) and leucovorin (200 mg/m2 in 1 hour) on day 1, followed by a continuous infusion of 5FU (2,600 mg/m2 in 48 hours), every 2 weeks. The objectives of the study were primarily to assess response rate and secondarily to evaluate the safety profile. Results: Fourteen patients were treated. Median age: 56 years (49–70). Performance status: 0 (n=4) and 1 (n=10). Median number of previous chemotherapy regimens: 5 (3–10) and previous platinum-based regimens: 2 (1–3). Median chemotherapy-free interval: 9.5 weeks (1–39). Median administered cycles of Folfox/patient: 8 (2–11 cycles). Responses according to RECIST criteria: 2 CR (14.5%), 2 PR (14.5%), 4 SD (29%) and 6 PD (43%). Responses according to CA125 Rustin's criteria: 4 CR (29%), 2 PR (14.5%), 5 SD (35.5%) and 3 PD (21%). Grade 1/2 and 3 peripheral neuropathy: 10 (71%) and 2 (14.5%), respectively. There were no grade 4 adverse events or deaths due to the treatment. Conclusions: Folfox is a valuable option for heavily pre-treated patients with ovarian cancer, with an overall response rate of 29% (95% CI 15.2% to 41.8%), disease stabilization in an additional 29%, and a manageable toxicity profile. These results support the use of Folfox as salvage treatment for patients with ovarian carcinoma. No significant financial relationships to disclose.

Phase II study of an optimized 5FU-oxaliplatin strategy (OPTIMOX2) with celecoxib in metastatic colorectal cancer: A GERCOR study

3554 Background: In the OPTIMOX study (André et al, ASCO 2003), 6 cycles of Folfox7 followed by simplified LV5FU2 maintenance were administered to decrease the neurotoxicity and to later allow FOLFOX7 reintroduction. Celecoxib is an anti-cox2 compound with anti-neoplastic properties such as angiogenic inhibition and apoptosis induction. We evaluated a new strategy exploring 1) the stop and go procedure (6 cycles of Folfox7 then stop and reintroduction Folfox7 at progression); 2) the addition of celecoxib during Folfox7 and chemotherapy-free interval (CFI). Methods: Patients (pts) with non resectable metastatic colorectal adenocarcinoma were treated in first-line by Folfox7: oxaliplatin 130 mg/m2 day (d1), and folinic acid 400 mg/m2 d1, and 5FU 46h 2400 mg/m2 every two weeks for 6 cycles. Chemotherapy was then interrupted and reintroduced at progression. Celecoxib 400 mg BID per os was administered during Folfox7 and CFI intervals until Folfox7 discontinuity for progression or limiting toxicity. 44 pts included, 42 eligible: Performans status (%) 0/1/2=45/43/12, median age 60 [31–76]. Half of patients had one metastatic site. Results: 42 pts are evaluable for safety and 41 for response. Grade 3–4 toxicity per pts (%) during the 6 first cycles of Folfox7 + celecoxib were neutropenia 5%, thrombocytopenia 17%, diarrhea 5%, nausea-vomiting 5%, neuropathy 2%, (maximal gr 3–4 toxicity 29%). During follow-up period (median 37 weeks), 2 pts presented grade 1–2 epigastralgia without ulcers and 1 digestive hemorrhage with gastritis. 1 CR, 15 PR (RR 39%; 95% CI: 24–54%), 18 SD (44%) and 7 PD (17%) were obtained (intent to treat). Median PFS was 28 weeks. 28/42 had a CFI (14 pts not evaluable for CFI: 5 metastasis resection after 3 months of therapy, 7 PD at 3 months of therapy, 2 out of protocol for toxicity). Median CFI duration was 72 days (range 29–147+) with 43% with PD after 2 months of CFI. Conclusions: In this phase II study, celecoxib combined with FOLFOX 7 is associated with a good safety and a response rate of only 39%. Pharmacokinetics and preclinical studies are needed to investigate potential interaction between celecoxib and FOLFOX 7 drugs. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Sanofi-Synthelabo Sanofi-Synthelabo

Combination of Cisplatin, Ifosfamide, and Irinotecan with rhG-CSF Support for the Treatment of Refractory or Relapsed Small-Cell Lung Cancer

Objective: This study was conducted in refractory or relapsed small-cell lung cancer to determine activity and toxicity of the combination of cisplatin, ifosfamide, and irinotecan with rhG-CSF support. Methods: Eighteen patients entered the trial. The median chemotherapy-free interval was 3.1 (range 1.0–14.5) months. Cisplatin (20 mg/m²) and ifosfamide (1.5 g/m²) were administered on days 1–4, and irinotecan (60 mg/m²) was administered on days 1, 8, and 15. In patients who experienced grade 4 hematological toxicity during the prior chemotherapy, the doses of cisplatin and irinotecan were reduced to 15 and 50 mg/m², respectively. After 10 patients were entered, cisplatin and irinotecan were administered at doses of 15 and 50 mg/m², respectively. This regimen was repeated every 4 weeks. rhG-CSF was administered subcutaneously at a dose of 50 μg/m² from days 50 to 18, except on the day of irinotecan treatment. Results: All patients could be assessed for response and toxicity. There were 1 complete and 16 partial responses, and an overall response rate of 94.4%. The median survival time of all patients was 339 days, and the 1-year survival rate was 47.5%. Hematological toxicities were significant. Grade 4 neutropenia and thrombocytopenia were observed in 61 and 33% of the patients, respectively. Diarrhea was mild and transient. There was no treatment-related death. Conclusion: The combination of cisplatin, ifosfamide, and irinotecan with rhG-CSF support was highly active for the treatment of refractory or relapsed small-cell lung cancer.