High dose-intensity of irinotecan administered every 3 weeks in advanced cancer patients: a feasibility study.

1997 ◽  
Vol 15 (3) ◽  
pp. 1080-1086 ◽  
Author(s):  
Y Merrouche ◽  
J M Extra ◽  
D Abigerges ◽  
R Bugat ◽  
G Catimel ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Dose Level ◽  
Advanced Cancer ◽  
Dose Intensity ◽  
Maximum Tolerated Dose ◽  
Unknown Primary ◽  
High Dose ◽  
Advanced Cancer Patients ◽  
Grade 3 ◽  
Febrile Episodes

PURPOSE To assess, on a multicenter basis, the feasibility of treating advanced cancer patients with high-dose irinotecan. PATIENTS AND METHODS Thirty-five patients who met the usual phase I criteria (26 men and nine women) were included. Primary tumor sites were colon, head and neck, unknown primary, kidney, liver, and others. All had been previously treated. Irinotecan was given at the maximum-tolerated dose (MTD) (600 mg/m2) or the level below (500 mg/m2) as a 30-minute infusion once every 3 weeks. RESULTS Eighteen patients were entered in the four participating centers at the MTD of 600 mg/m2. This dose level was clearly shown not to be feasible: 14 patients (78%) had grade 3 to 4 neutropenia, with febrile episodes in 11 patients; grade 3 to 4 diarrhea was observed in nine patients; and one toxic death occurred. Subsequently, 17 not heavily pretreated patients were included at 500 mg/m2 and carefully monitored. The safety of this dose level was considered acceptable: 41% of patients had grade 3 to 4 neutropenia, 24% experienced grade 3 to 4 diarrhea, and no febrile granulocytopenia or toxic death occurred. Six partial responses were documented in metastatic colorectal cancer, all in patients who had previously received conventional chemotherapy, four in patients who had exhibited progressive disease under fluorouracil (5FU)-based chemotherapy. CONCLUSION We plan to study the higher dose-intensity 500-mg/m2 level on good-risk and carefully monitored patients. This could enlarge the spectrum of tumors sensitive to irinotecan and improve the already good results observed in colorectal cancers.

Phase I dose and schedule finding study of pegylated liposomal doxorubicin (D) and weekly docetaxel (T)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12012-12012 ◽  
Author(s):  
O. S. Shaye ◽  
A. B. El-Khoueiry ◽  
A. Garcia ◽  
D. Wei ◽  
S. Groshen ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Level ◽  
Metastatic Breast ◽  
Pegylated Liposomal Doxorubicin ◽  
Dose Intensity ◽  
Median Number ◽  
Maximum Tolerated Dose ◽  
Salivary Gland Carcinomas ◽  
Common Grade ◽  
Grade 3

12012 Background: The combination of D and T has many potential applications, particularly in breast and ovarian cancers. A phase 3 trial is examining D + T versus T in first-line metastatic breast cancer ( NCT00091442 ). D has better tumor localization and penetration in solid tumors than conventional doxorubicin. In previous studies, the maximum tolerated dose (MTD) of the combination was identified as D 30 mg/m2 and T 75 mg/m2 q4 weeks (wks), with a recommended dose and schedule of D 30 mg/m2 and T 60 mg/m2 q3wks without G-CSF. We conducted a phase I study to determine the MTD of D with weekly T. Our hypothesis was that the lower incidence of myelosuppression with weekly T would allow for higher doses of both drugs. Methods: There were 2 schedules. Arm A: D q4wks starting at 25 mg/m2 with weekly T for 3 wks starting at 30 mg/m2. Arm B: D q2wks starting at 15 mg/m2 with weekly T for 3 wks starting at 30 mg/m2. One cycle was 28 days. Standard 3+3 design was used with MTD defined as the highest dose level causing dose limiting toxicity (DLT) in ≥ 2/6 patients (pts). Results: 32 pts were treated; 13 females, 19 males, median age of 60 years. Median number of cycles administered was 2 (1–13) with a median follow-up of 11.5 months. Tumor types included lung (16%), thyroid (9%), esophagus (9%), nasopharynx, breast, colorectal, stomach and kidney (6% each). Arm A (13 pts) was closed after 2/7 evaluable pts at dose level 2 (D 33mg/m2; T 30 mg/m2) experienced DLT in the form of grade 3 stomatitis. The most common grade 3/4 toxicities were neutropenia (3/13), stomatitis (3/13) and fatigue (3/13). Arm B accrued 19 pts. The trial was closed at the highest planned dose in Arm B (D 20mg/m2 q2wks and T 35 mg/m2 weekly) with only 1/6 evaluable pts experiencing DLT in the form of grade 4 fatigue and weakness. The most common grade 3/4 toxicities in Arm B included neutropenia (5/19 pts), fatigue (5/19 pts) and stomatitis (2/19 pts). There was no grade 3/4 hand-foot syndrome or cardiotoxicity. 2 partial responses were observed in nasopharyngeal and salivary gland carcinomas, with 13 pts achieving stable disease. Conclusions: The combination of D q2 wks and T weekly for 3/4 wks is well tolerated and results in a higher dose intensity of both drugs than in previously evaluated regimens. [Table: see text]

Combined abiraterone, salvage prostate bed radiotherapy and LH-RH agonists (CARLHA) in biochemically-relapsing prostate cancer patients following prostatectomy: A phase I study of the GETUG/GEP.

2017 ◽  
Vol 35 (6_suppl) ◽  
pp. 45-45 ◽  
Author(s):  
Stephane Supiot ◽  
Loic Campion ◽  
Pascal Pommier ◽  
Melanie Dore ◽  
Severine Racadot ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Dose Level ◽  
Liver Toxicity ◽  
Maximum Tolerated Dose ◽  
Abiraterone Acetate ◽  
Recommended Dose ◽  
Level 1 ◽  
Grade 3 ◽  
Lh Rh

45 Background: Salvage radiotherapy (RT) plus 6 months LH-RH therapy (ADT) improves biochemical relapse free survival in men with rising PSA following prostatectomy. Abiraterone acetate (Aa) increases overall survival in metastatic prostate cancer. We aimed to establish the toxicity of adding Aa combined with salvage RT and 6 months goserilin (Gos). Methods: We enrolled pT2-pT4a pN0 prostate cancer patients (pts) with rising PSA (0.2 to <2.0 μg/l) following radical prostatectomy. The primary endpoint was to determine the Maximum Tolerated Dose and recommended dose of Aa during RT plus Gos, two dose levels tested : 1 (750mg) and 2 (1000 mg). Two different schemes were explored: Sheme A: Aa (1000 mg) and predisone (10 mg) were given orally during 1 month to salvage IMRT (66 Gy in 33 fractions). The first day of irradiation, Aa is reduced to level 1 or 2 and 10.8 mg Gos is injected (sc). In sheme B, Gos is injected the first day (1 month before starting RT). Results: We recruited 9 + 9 pts in scheme A and B respectively. In scheme A, Testosterone (Tst) levels declined to castration level (<0.5ng/ml) after 10 days . Two/9 pts did not achieve castration levels at 30 days. Median LH levels increased to 10.4 (D10) and 12.5 IU/l (D20). At dose level 1, 4/9 pts (44%) experienced grade 3 hepatitis, occurring prior to RT or during RT (8 Gy, 36 and 54 Gy). We hypothesized that this unexpected liver toxicity was related to the LH increase during the first month (Aa administration without Gos). Therefore, we modified LH-RH administration (scheme B) and recruited 9 more pts. Tst levels dropped to undetectable at day 6, while median LH levels decreased to 6.1 (D10) and 1.7 IU/l (D20). At dose level 1 (3 + 3 pts), no grade 3 liver toxicity was reported. No other grade 3 toxicity was recorded. At dose level 2, 2/3 pts had grade 3 hepatitis occurring during RT. CYP17 polymorphism did not correlate with liver toxicity. Conclusions: The recommended dose of Aa combined to short-term androgen deprivation and salvage RT is 750 mg. Aa alone did lead to castration levels in 22% of pts.An unexpected high frequency of grade 3 liver toxicity was observed. Clinical trial information: NCT01780220.

Impact of Five Prophylactic Filgrastim Schedules on Hematologic Toxicity in Early Breast Cancer Patients Treated With Epirubicin and Cyclophosphamide

2005 ◽  
Vol 23 (28) ◽  
pp. 6908-6918 ◽  
Author(s):  
Paola Papaldo ◽  
Massimo Lopez ◽  
Paolo Marolla ◽  
Enrico Cortesi ◽  
Mauro Antimi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Early Breast Cancer ◽  
Dose Intensity ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Breast Cancer Patients ◽  
Nonrandomized Trial ◽  
Grade 3 ◽  
To Receive

Purpose To evaluate the comparative efficacy of varying intensity schedules of recombinant human granulocyte colony-stimulating factor (G-CSF; filgrastim) support in preventing febrile neutropenia in early breast cancer patients treated with relatively high-dose epirubicin plus cyclophosphamide (EC). Patients and Methods From October 1991 to April 1994, 506 stage I and II breast cancer patients were randomly assigned to receive, in a factorial 2 × 2 design, epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 intravenously on day 1 every 21 days for 4 cycles ± lonidamine ± G-CSF. The following five consecutive G-CSF schedules were tested every 100 randomly assigned patients: (1) 480 μg/d subcutaneously days 8 to 14; (2) 480 μg/d days 8, 10, 12, and 14; (3) 300 μg/d days 8 to 14; (4) 300 μg/d days 8, 10, 12, and 14; and (5) 300 μg/d days 8 and 12. Results All of the G-CSF schedules covered the neutrophil nadir time. Schedule 5 was equivalent to the daily schedules (schedules 1 and 3) and to the alternate day schedules (schedules 2 and 4) with respect to incidence of grade 3 and 4 neutropenia (P = .79 and P = .89, respectively), rate of fever episodes (P = .84 and P = .77, respectively), incidence of neutropenic fever (P = .74 and P = .56, respectively), need of antibiotics (P = .77 and P = .88, respectively), and percentage of delayed cycles (P = .43 and P = .42, respectively). G-CSF had no significant impact on the delivered dose-intensity compared with the non–G-CSF arms. Conclusion In the adjuvant setting, the frequency of prophylactic G-CSF administration during EC could be curtailed to only two administrations (days 8 and 12) without altering outcome. This nonrandomized trial design provides support for evaluating alternative, less intense G-CSF schedules for women with early breast cancer.

Medroxyprogesterone acetate (MAP) plasma levels after multiple high-dose administration in advanced cancer patients

1983 ◽  
Vol 11 (1) ◽  
Author(s):  
CarloMaurizio Camaggi ◽  
Elena Strocchi ◽  
Michele Giovannini ◽  
Bruna Angelelli ◽  
Barbara Costanti ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Advanced Cancer ◽  
Medroxyprogesterone Acetate ◽  
Plasma Levels ◽  
High Dose ◽  
Advanced Cancer Patients ◽  
Dose Administration

Safety and pharmacokinetics (PK) of AMG 706 in combination with panitumumab and gemcitabine-cisplatin in patients (pts) with advanced cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 14057-14057 ◽  
Author(s):  
J. Crawford ◽  
H. Burris ◽  
J. Stephenson ◽  
G. Otterson ◽  
M. Stein ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Advanced Cancer ◽  
Objective Response ◽  
Maximum Tolerated Dose ◽  
Dose Finding ◽  
Unknown Primary ◽  
Open Label ◽  
Prior Chemotherapy ◽  
Label Dose ◽  
Grade 3

14057 Background: AMG 706 is an oral, investigational multikinase (MKI) inhibitor with antiangiogenic and direct antitumor activity that selectively targets VEGF, PDGF and Kit receptors. Methods: This is an ongoing phase 1b, open-label, dose-finding study of AMG 706 plus panitumumab and gemcitabine-cisplatin. Objectives are to establish the maximum tolerated dose and to assess safety, objective response and PK of AMG 706 with this regimen. Pts =18 yrs with advanced cancer, ECOG 0–1, =1 prior chemotherapy for advanced disease and no prior oral VEGFr MKIs or anti EGFR therapy, received panitumumab (9mg/kg IV day 1 of each 3-wk cycle) plus gemcitabine (1250mg/m2 IV days 1 and 8) and cisplatin (75mg/m2 IV day 1), and escalating doses of AMG 706 given continuously from day 1 of cycle 1. Assessments included dose-limiting toxicities (DLT; cycle 1), PK and tumor response (every 6–9 wks from wk 6). Results: As of Nov 2006, 36 pts (NSCLC n=19; pancreatic cancer n=4; other n=10; unknown primary n=3) were enrolled; 42% had prior chemotherapy. There was 1 DLT: pulmonary embolism, grade 5 (50mg QD). Selected treatment-related adverse events in =10% of pts are shown in the table . 39% of pts receiving AMG 706 had thromboembolic events (TE); 25% receiving study therapy without AMG 706 had TEs. There was 1 case of cholecystitis (grade 1), 1 of gallbladder pain (grade 3). Preliminary data showed that AMG 706 PK at 125 mg QD was comparable to data from monotherapy studies at the same dose level. Based on 29 pts with available response data (too early to evaluate/data unavailable n=7), objective tumor responses per RECIST were: CR n=1, 3% (breast cancer); PR n=9, 31% (NSCLC n=6; pancreatic cancer n=2; unknown primary n=1); SD n=17, 59%; PD n=1, 3%. Conclusions: In this study of pts with advanced cancer, AMG 706 was tolerable when combined with panitumumab and gemcitabine-cisplatin, with little effect on AMG 706 PK. Further studies need to determine if the observed TE rate exceeds gemcitabine-cisplatin background rates. [Table: see text] No significant financial relationships to disclose.

Phase I study of bi-weekly pemetrexed (P) plus cisplatin (C) in patients with advanced cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2580-2580
Author(s):  
A. Lopez-Martin ◽  
L. Paz-Ares ◽  
E. Calvo ◽  
D. Castellano ◽  
C. Valverde ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Dose Level ◽  
Malignant Tumors ◽  
Locally Advanced ◽  
Dose Intensity ◽  
Maximum Tolerated Dose ◽  
Fixed Dose ◽  
Unknown Primary ◽  
Clinical Activity ◽  
Metastatic Urothelial Cancer

2580 Background: Cisplatin and pemetrexed have demonstrated clinical activity in several malignant tumors including mesothelioma and non small cell lung cancer. There is preclinical evidence of synergism between both agents as well as clinical non-overlapping toxicities, thus providing the rationale for their evaluation in combination. Our aim was to develop a well-tolerated combination of bi-weekly CP able to deliver higher dose intensity than the every 3-week standard. Methods: Escalating doses of P from a starting dose level of 300 mg/m2, with a fixed-dose of C 50 mg/m2, both biweekly on 28-day cycles, were administered to patients with refractory advanced solid malignancies and calculated creatinine clearance = 45 mL/min. Results: Twenty one patients (5 female/16 male); median age 61 (39–76); ECOG 0 (16), 1 (5); lung cancer (9); soft-tissue sarcoma (3); unknown primary, bladder, breast, rectum, esophagus, melanoma, mesothelioma, prostate, and tonsil (1, each) have received a total of 48 courses (median 2, range 0–5), at P dose levels of 300 mg/m2 [8 pts, Dose level 1 (DL1)], 400 mg/m2 (7 pts, DL2), and 500 mg/m2 (6 pts, DL3), with full doses of C. Four patients were non-evaluable (2 at DL1, 1 at DL2 and 1 at DL3) because of early PD (2) and non-drug related serious adverse event (2 pt). Dose Limiting Toxicities (DLT) were G4 neutropenia (1 pt) at 300 mg/m2; and prolonged G 1/2 thrombocytopenia (1 pt) at 500 mg/m2. There were also 2 pts with non-DLT G4 neutropenia at DL3. The rest of toxicities were mild to moderate being the most frequent asthenia, nausea, anorexia, stomatatis, and sensory neuropathy. DL3 was considered the Maximum Tolerated Dose (MTD) and the previous level with P at 400 mg/m2 was declared the recommended phase II dose. Three additional patients were treated at DL2 for dose confirmation. A PR has been observed in 2 pts with NSCLC, 1 pt with breast, and 1 with esophagus cancer. Conclusions: Biweekly administration of pemetrexed (400 mg/m2) plus cisplatin (50 mg/m2) is clinically well tolerated and can be used safely. The regimen delivers higher dose intensity of P and equal of C as the standard. This regimen is currently being studied in a phase 2 trial in patients with locally advanced, non resectable or metastatic urothelial cancer. No significant financial relationships to disclose.

The validity of EORTC QLQ-C30 fatigue scale in advanced cancer patients and cancer survivors

2003 ◽  
Vol 17 (8) ◽  
pp. 664-672
Author(s):  
Heidi Knobel ◽  
Jon HaKvard Loge ◽  
Elisabeth Brenne ◽  
Peter Fayers ◽  
Marianne Jensen Hjermstad ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Advanced Cancer ◽  
Metastatic Cancer ◽  
Randomized Study ◽  
Ceiling Effect ◽  
High Dose ◽  
Advanced Cancer Patients ◽  
Specific Instrument ◽  
Eortc Qlq C30 ◽  
Eortc Qlq

Fatigue is a major complaint among advanced cancer patients. Several instruments are available for measuring fatigue. The EORTC QLQ-C30 is one of the most frequently used health-related quality of life (HRQOL) instruments, and it includes a three-item fatigue subscale. Limited knowledge exists about the validity, performance and sensitivity of EORTC QLQ-C30 fatigue scale as compared with a fatigue-specific instrument. The aim of the present study was to validate the EORTC QLQ-C30 fatigue scale (FA) against the Fatigue Questionnaire (FQ). The FQ is frequently used and was developed to measure fatigue in both cancer and noncancer populations. The FQ measures physical (PF, seven items) and mental fatigue (MF, four items). The study population included two different cohorts: A) patients with advanced metastatic cancer included in a prospective randomized study of palliative radiotherapy ( n = 238); B) patients with leukaemia and malignant lymphoma curatively treated with stem-cell transplantation and high-dose chemotherapy ( n = 128). The analysis demonstrated that the FA correlated higher with the PF scale (r = 0.67–0.75) as compared with the MF scale (r = 0.49–0.61). The item–scale correlations between FA items and the PF scale were consistently higher than between FA items and the MF scale. A factor analysis including all the items within the FA and the FQ identified two factors. All FA items loaded on a PF factor (0.70–0.85). A floor/ ceiling effect, indicating a high number of respondents with lowest, respectively, highest scores was observed more frequently in the FA as compared with the FQ. The PF discriminated better between diagnostic groups with different levels of fatigue than the FA did. In conclusion, the EORTC QLQ-C30 fatigue scale is measuring physical fatigue. A floor/ ceiling effect seems to appear for the EORTC QLQ-C30 fatigue scale. The validity of the EORTC QLQ-C30 fatigue scale is to be questioned for use in palliative care patients. In studies with fatigue as a defined end point, a domain-specific instrument should, therefore, be added.

Increasing Single Epirubicin Doses in Advanced Soft Tissue Sarcomas

2002 ◽  
Vol 20 (5) ◽  
pp. 1329-1334 ◽  
Author(s):  
Massimo Lopez ◽  
Patrizia Vici ◽  
Luigi Di Lauro ◽  
Silvia Carpano
Keyword(s):  
Soft Tissue ◽  
Dose Level ◽  
Response Rate ◽  
Soft Tissue Sarcomas ◽  
Dose Intensity ◽  
Maximum Tolerated Dose ◽  
High Dose ◽  
Median Response ◽  
The Third ◽  
Dose Levels

PURPOSE: To evaluate the maximum-tolerated dose and the clinical efficacy of epirubicin in patients with advanced soft tissue sarcoma. PATIENTS AND METHODS: Sixty-one patients were treated at three different epirubicin dose levels: 140 mg/m2 (six patients), 160 mg/m2 (52 patients), and 180 mg/m2 (three patients). Cycles were repeated every 3 weeks for a maximum of eight cycles. The first two dose levels proved to be feasible and safe without dose-limiting toxicity (DLT). Because the first three patients entering the third dose level experienced DLT, subsequent patients received the next lower dose level. RESULTS: The overall response rate was 44% (95% confidence interval, ± 12%), with six complete (10%) and 21 partial (34%) responses. Responses seemed related to epirubicin dose level, because the response rate was 17%, 44%, and 100% for the three dose levels (χ2 test for trend, P = .02). Median response duration, median time to progression, and median overall survival were 10, 8, and 15 months, respectively. Myelosuppression was the most frequent side effect, with grade 3 or 4 neutropenia occurring in 79% of the patients; 31% of patients were febrile. Nonhematologic toxicity was mainly grades 1 and 2. The mean epirubicin dose-intensity was 49 mg/m2 per week. CONCLUSION: The third epirubicin dose level (180 mg/m2) was the maximum-tolerated dose. The recommended drug dose for clinical use is 160 mg/m2 every 3 weeks with hematopoietic support. Single high-dose epirubicin is effective as first-line treatment and should be preferentially used whenever a high response rate is important to allow the resection of an otherwise unresectable disease or whenever it might result in a significant symptomatic benefit.

Sign in / Sign up

Export Citation Format

Share Document