Median RDI Research Articles

Biweekly administration of irinotecan (CPT-11), oxaliplatin (OX) and 5-fluorouracil (5-FU) as first-line treatment of advanced or metastatic colorectal cancer (MCRC)

3561 Background: Triple combination chemotherapy of CPT-11, OX, and 5-FU has been shown to be active and safe in MCRC. We design the present study based on the assumption that the biweekly administration of the three agents could improve the safety profile of this schedule. Secondary objectives were to determine ORR, TTP and OS achieved. Methods: Patients with histological confirmation of MCRC, measurable disease, ECOG PS ≤ 2 and adequate bone marrow, renal and hepatic functions were included. Previous adjuvant chemotherapy was allowed if finished at least 6 months before starting study treatment. Patients received OX (85 mg/m2, iv, D1) followed by CPT-11 (150 mg/m2, iv, D1) and 5-FU (1000 mg/m2/day, ci, D1–4). Cycles were repeated every 2 weeks until progressive disease, excessive toxicity or consent withdrawal. Results: Fifty patients were enrolled (M/F, 34/16), median age 60 (30–74) and 94% had ECOG 0–1 PS. Primary tumour sites were colon (64%), rectum (34%) or both (2%). Median number of metastatic lesion sites was 1 (29% with ≥2 sites), mainly located in liver (73%), lung (27%) and lymph nodes (10%). 14% of patients received previous adjuvant chemotherapy. A total of 385 cycles (median 8, range 1–16) were administered. Median RDI was 86%, 86% and 84% for OX, CPT-11 and 5-FU, respectively. All patients were evaluable for toxicity. Main grade 3/4 toxicity per cycle was neutropenia (5%), diarrhoea (5%), stomatitis (4%), asthenia/fatigue (4%) and nausea/vomiting (3%). Febrile neutropenia was observed in 1 patient and in 1 cycle. There was 1 treatment related death due to a septic shock after the first cycle. Efficacy: In 43 evaluable patients, 9 achieved CR, 22 PR, 8 SD and 4 PD, resulting in an ORR of 72% (95% CI: 59–86) and a tumour growth control (RR + SD) of 91%. With a median follow-up of 12.8 months, TTP and OS were 11.3 months (95% CI: 8.2–13.9) and 18.4 months (95% CI: 14.9–26.9), respectively. Conclusions: Biweekly administration of OX, CPT-11 5-FU is an active regimen with a manageable toxicity profile as first-line treatment in patients with advanced or metastatic CRC. No significant financial relationships to disclose.

Biweekly administration of irinotecan (CPT-11), oxaliplatin (OX) and 5-fluorouracil (5-FU) as first-line treatment of advanced or metastatic colorectal cancer (MCRC)

3561 Background: Triple combination chemotherapy of CPT-11, OX, and 5-FU has been shown to be active and safe in MCRC. We design the present study based on the assumption that the biweekly administration of the three agents could improve the safety profile of this schedule. Secondary objectives were to determine ORR, TTP and OS achieved. Methods: Patients with histological confirmation of MCRC, measurable disease, ECOG PS ≤ 2 and adequate bone marrow, renal and hepatic functions were included. Previous adjuvant chemotherapy was allowed if finished at least 6 months before starting study treatment. Patients received OX (85 mg/m2, iv, D1) followed by CPT-11 (150 mg/m2, iv, D1) and 5-FU (1000 mg/m2/day, ci, D1–4). Cycles were repeated every 2 weeks until progressive disease, excessive toxicity or consent withdrawal. Results: Fifty patients were enrolled (M/F, 34/16), median age 60 (30–74) and 94% had ECOG 0–1 PS. Primary tumour sites were colon (64%), rectum (34%) or both (2%). Median number of metastatic lesion sites was 1 (29% with ≥2 sites), mainly located in liver (73%), lung (27%) and lymph nodes (10%). 14% of patients received previous adjuvant chemotherapy. A total of 385 cycles (median 8, range 1–16) were administered. Median RDI was 86%, 86% and 84% for OX, CPT-11 and 5-FU, respectively. All patients were evaluable for toxicity. Main grade 3/4 toxicity per cycle was neutropenia (5%), diarrhoea (5%), stomatitis (4%), asthenia/fatigue (4%) and nausea/vomiting (3%). Febrile neutropenia was observed in 1 patient and in 1 cycle. There was 1 treatment related death due to a septic shock after the first cycle. Efficacy: In 43 evaluable patients, 9 achieved CR, 22 PR, 8 SD and 4 PD, resulting in an ORR of 72% (95% CI: 59–86) and a tumour growth control (RR + SD) of 91%. With a median follow-up of 12.8 months, TTP and OS were 11.3 months (95% CI: 8.2–13.9) and 18.4 months (95% CI: 14.9–26.9), respectively. Conclusions: Biweekly administration of OX, CPT-11 5-FU is an active regimen with a manageable toxicity profile as first-line treatment in patients with advanced or metastatic CRC. No significant financial relationships to disclose.

Vinorelbine (NVB)-carboplatin (CBDCA) vs non-platinum doublets in inoperable non-small cell lung cancer (NSCLC) patients (pts)-final results of the Glob 2 phase III with patient benefit analysis

7016 Background: NVB-CDDP is used as a standard regimen for pts with NSCLC. Regimens in which CDDP is replaced by CBDCA or a non Platinum (P) cytotoxic, may result in more favourable tolerance and convenience This phase III was set up to compare a P based regimen (NVB-CBDCA) to a non-P based regimen (NVB-GEM). Methods: Inoperable NSCLC pts were randomly assigned to q3w cy in Arm A (A): NVB 30 mg/m2 at D1,8+CBDCA AUC 5 at D1 or Arm B (B): NVB 25 mg/m2+GEM 1000 mg/m2 both given at D1,8 with 150 evaluable pts planned in each arm. Objective response (OR) was the primary endpoint with secondary end points being time related parameters/tolerance and clinical benefit evaluated on 6 cancer symptoms evolution taking into account weight and PS changes. Results: 316 pts were recruited in 2 yrs in 31 centres with 159 pts in A and 157 in B. Groups were well balanced with same median age: 60/59y, KPS: 90–100 in 63/69%. In both arms pts were metastatic at inclusion in 80%. A median number of 4 cy was given. Median RDI for NVB was 91% (A) and 94% (B) with median RDI for CBDCA at 94% and GEM at 93%. OR in ITT after review was 20.8% (DC=66%) in A vs 28% (DC=72.6%) in B (p=0.15). At the cut-off date (April 1st, 2003), median follow-up was 21.5 m with 128/110 deaths in A/B. MS was 8.6m for A vs 11.5m for B with 1 year survival respectively at 34.4% and 48.9% (p=0.01) and PFS at 3.9 and 4.4m. Main gr3–4 haematological AEs by pts in A/B, were: neutropenia in 44.5/23.4% and significantly more febrile neutropenia in A (17pts/19cy) vs B (1pt/1cy) with 4/0 toxic deaths respectively. There were less gr3–4 non-hematological tox reported in B. Regarding clinical benefit, fatigue, appetite, cough and dyspnea improvement were better in B. Chest pain and hemoptysis improvement were similar in both arms. Mean weight was stable in both. On 111 evaluable pts for the clinical benefit in A, response rate was 32.4% compared to 40.9% (p=0.19) in 110 evaluable pts in B. Conclusions: NVB-GEM given as a non-P doublet in this phase III has demonstrated OR, PFS and clinical benefit comparable to NVB–CBDCA doublet with a favorable MS and tolerance profile. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Pierre Fabre

Biweekly irinotecan (CPT-11) plus 5-FU as first-line chemotherapy for elderly patients with metastatic colorectal cancer (MCRC). Final results of the Spanish Digestive Group (TTD) study

3597 Background: Elderly patients are frequently excluded from clinical studies due to comorbidity. However, clinical trials in this setting are needed to avoid extrapolating the results obtained in a younger population. We designed this study to evaluate the RR of a standard first-line therapy in elderly patients with MCRC. Secondary objectives were safety profile, TTP and OS Methods: Patients ≥ 72 years old with histologically confirmed MCRC, measurable disease, ECOG <2, adequate bone marrow, renal and hepatic function were included. Previous chemotherapy for advanced disease, CNS involvement or geriatric syndromes were not allowed. Treatment: CPT-11, 180 mg/m2 and 5-FU, 3 g/m2 as a 48h ci, were administered biweekly until progressive disease, unbearable toxicity or consent withdrawal Results: 91 patients were included and 85 were evaluable. Median age of 77 (72–85), male/female (51/34) and ECOG PS 0–1: 100%. Primary tumor sites were colon (67%), rectum (32%) or both (1%). Main comorbidities were hypertension (46%), diabetes (18%), cardiopathy (17%) and chronic pulmonary disease (8%). Median No. of metastatic locations was 1 (33% with ≥2 sites) mainly located in liver (77%) and lung (27%). 28% of patients received previous adjuvant chemotherapy. Up to date, 919 cycles (median 12, range 1–26) were administered, with a median RDI of 91% for both CPT-11 and 5-FU. 85 patients were evaluable for toxicity. Grade 3/4 toxicity per patient were neutropenia (21%), diarrhea (17%), asthenia (13%), leukopenia (8%), abdominal pain (7%) and vomiting (6%). Only 1 patient had febrile neutropenia in 1 cycle. There were 2 treatment related deaths (diarrhea n=1, and digestive hemorrhage n=1). Efficacy: On an ITT analysis of 85 patients, 3 achieved CR, 27 PR, 28 SD and 15 progressed, resulting in an ORR of 35 % (95% CI: 25–46) and tumour growth control (RR + SD) in 68% of patients. With a median follow-up of 10.9 months, TTP was 8.0 months (95% CI: 6.1–9.9) and OS was 15.1 months (95% CI: 13.3–16.9) Conclusions: CPT-11 plus 5-FU is an active and feasible treatment for patients older than 72 years old with MCRC. No significant financial relationships to disclose.

Autonomic Stress Tests in Obstructive Sleep Apnea Syndrome and Snoring

Apneic events in the obstructive sleep apnea syndrome (OSAS) are associated with cardiovascular responses mediated through the autonomic nervous system. We examined autonomic cardiovascular responses in 33 patients (median age = 50 years, range = 20-72 years) undergoing polysomnography for suspected OSAS. We examined these responses in the evening and at arousal in the morning. Tests consisted of heart rate responses to Valsalva maneuver, deep breathing and change from lying down to standing. In addition, systolic blood pressure (BP) response to standing and diastolic BP response to handgrip were studied. Each abnormal test scored +1 and each marginal result +0.5. Autonomic nervous system (ANS) test results were scored as abnormal if a subject had a score > 1 which included at least one abnormal test. The total scores for evening and morning tests combined showed 11/24 sets of scores > 1 in 12 severe OSAS patients [median RDI (apnea+hypopnea per hour slept) = 44 (range = 31-74)] compared to 3/22 in non-OSAS (p = 0.04). The response to deep breathing, expressed as an expiratory to inspiratory ratio (E/I), was the test most often found abnormal. A significant difference between normal abnormal autonomic stress test (AST) groups was observed in the evening and the morning as regards cumulative time spent under 90% SaO2 and minimal SaO2. We conclude that abnormal autonomic stress responses are common in OSAS and are probably a secondary defect.