Final results of a FNCLCC French Sarcoma Group multicenter randomized phase II study of gemcitabine (G) versus gemcitabine and docetaxel (G+D) in patients with metastatic or relapsed leiomyosarcoma (LMS)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 10527-10527
Author(s):  
P. Pautier ◽  
B. Bui Nguyen ◽  
N. Penel ◽  
S. Piperno-Neumann ◽  
C. Delcambre-Lair ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Soft Tissue Sarcomas ◽  
Median Number ◽  
Tumor Location ◽  
Pelvic Radiotherapy ◽  
Randomized Phase Ii ◽  
Number Of Cycles ◽  
Dose Reductions

10527 Background: An objective response rate (RR) of 8% and 17% with G and G+D were respectively reported in metastatic soft tissue sarcomas (Maki, J Clin Oncol. 2007). We previously reported a 5% RR in 41 evaluable patients (pts) with ‘non uterus‘ LMS randomized to each arm of this randomized phase II study (Duffaud, ASCO. 2008). We present here the results of G vs G+D in uterine and all LMS. Methods: Patients had histologically proven metastatic or unresectable LMS, one prior anthracycline- based regimen, age ≥18, measurable disease (RECIST), PS ≤ 2. Treatment was G 1,000 mg/m2(over 100 minutes, d1+d8+d15) q28 days (d) or G 900 mg/m2(over 90 min, d1+d8) and docetaxel 100 mg/m2 (over 60 min, d8) q21 days; in the G+D arm, pts received lenograstim d9–15, 25% dose reductions were employed for prior pelvic radiation. The primary endpoint was the objective RR (CR+PR), evaluated every 2 cycles. Stratification was by primary tumor location (uterus vs. non-uterus). The Simon method was used: for “uterus” study, 20 pts per arm for a 74% probability of selecting the arm with a real RR of 50%, expected baseline RR was 40%; for the “non-uterus” study, 20 pts per arm for a 92% probability of selecting the arm with a real RR of 40%, expected baseline RR was 20%. Results: From 02/06 to 12/08, 44 pts were enrolled in the “non-uterus” study, 40 pts in the “uterus” study. Currently 76/82 pts are evaluable for response (41/44 in the “non uterus” and 35/38 in the “uterus” study) and 80/84 for toxicity. In the uterus group the median age is 57 (range 41–80), 24 pts received prior pelvic radiotherapy, the median number of cycles was 5 (range 0–8) and dose received/dose planned (%) were 69% in G arm, 88% of G and 86% of D in G+D arm. No differences in toxicity were observed between both LMS locations: in the G arm, toxicity was moderate except for one pulmonary gr4; in the G+D arm one toxic death was related to gr5 thrombocytopenia and there were 2 non-haemathologic gr4 toxicities; 11 pts stopped for intolerable toxicity (3 in G and 8 in G+D arm) and 1 pt for hypersensitivity (G+D arm). Conclusions: Final tumor response for uterine LMS and updated toxicity and PFS data for all the LMS will be presented during the meeting. [Table: see text]

Updated results from a randomized phase II dose-ranging study of the JAK2-selective inhibitor SAR302503 in patients with myelofibrosis (MF).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7109-7109 ◽  
Author(s):  
Animesh Dev Pardanani ◽  
Catriona H. M. Jamieson ◽  
Nashat Y. Gabrail ◽  
Claudia Lebedinsky ◽  
Guozhi Gao ◽  
...  
Keyword(s):  
High Risk ◽  
Phase Ii ◽  
Median Number ◽  
Randomized Phase Ii ◽  
Night Sweats ◽  
Dose Ranging ◽  
Grade 3 ◽  
Number Of Cycles ◽  
Dose Reductions ◽  
Unacceptable Toxicity

7109 Background: We previously reported results of treating MF patients with 3 cycles of 300, 400, or 500 mg of SAR302503 (NCT01420770; Blood 2012;120:21 Abs 2837). This is a report of efficacy and safety after 6 cycles. Methods: Patients ≥18 years of age with intermediate-2 or high-risk MF and splenomegaly were eligible. SAR302503 is administered orally, once a day in consecutive 4-week cycles until disease progression or unacceptable toxicity. Spleen response (≥35% reduction in spleen volume vs baseline) was assessed by MRI/CT (blinded independent central review). Results: 31 patients were enrolled (n=10 in the 300 and 400 mg groups; n=11 to 500 mg). Risk status was balanced in all but the 300 mg group (70% high-risk). Most patients were JAK2V617F positive (90%) and blood transfusion independent (81%). Spleen response rates at the end of cycle (EOC) 6 (secondary end point) were 30% (3/10) in the 300 mg group, 60% (6/10) with 400 mg, and 55% (6/11) with 500 mg compared with EOC 3 rates of 30%, 50%, and 64%, respectively. One patient on 500 mg who had a spleen response at EOC 3 (39% reduction), but not at EOC 6 (25% reduction) had dose reductions to 200 mg due to anemia. Median number of cycles was 13 (range, 2–17) and 24 patients have been on treatment >12 months. SAR302503 reduced baseline constitutional symptoms at the EOC 3, with the greatest responses for night sweats in 14/15 patients (93%), itching 10/14 (71%), early satiety and abdominal pain, each in 10/18 (56%). Most common adverse events were anemia and diarrhea, with grade 3–4 rates of 58% and 13%, respectively. The rate of grade 3–4 thrombocytopenia was 16%. There was no grade 3–4 neutropenia. The diarrhea rate tended to decrease after the first 2 treatment cycles. There have been no reports of withdrawal syndrome after stopping SAR302503. Median JAK2V617F allele burden was 93% at baseline, 87% at the EOC 3, and 78% at EOC 6 in 19/26 patients who had available samples. The expression of 22 of 97 cytokines was significantly regulated (≥1.5 fold difference; p<0.05) after cycle 1. Conclusions: In this Phase II trial, continued treatment with SAR302503 was associated with clinically meaningful reductions in splenomegaly. Symptom data will be updated. Clinical trial information: NCT01420770.

A randomized phase II study of a combination of docetaxel and S-1 versus docetaxel monotherapy in pts with NSCLC previously treated with platinum-based chemotherapy: Results of Okayama Lung Cancer Study Group (OLCSG) trial 0503

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8058-8058
Author(s):  
Y. Segawa ◽  
K. Hotta ◽  
N. Takigawa ◽  
K. Matsuo ◽  
H. Yoshioka ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Median Number ◽  
Lung Cancer Study Group ◽  
Randomized Phase Ii ◽  
Platinum Based Chemotherapy ◽  
Grade 3 ◽  
Line Setting ◽  
Ecog Ps

8058 Background: Recent studies have demonstrated that docetaxel (DOC) monotherapy provides a significant survival prolongation in relapsed pts with NSCLC. However, its benefit remains modest and further improvement is needed. S-1 is a newly developed oral 5-fluorouracil derivative, possessing a promising anti-tumor activity in NSCLC. Based on a superior effect of combination of DOC and 5-fluorouracil derivative (capecitabine) to DOC alone in anthracycline-pretreated breast cancer pts, we conducted a randomized phase II study to evaluate the clinical significance of adding S-1 to DOC in the second-line setting. Methods: Pts with relapsed NSCLC to the first-line platinum-based chemotherapy were randomly allocated to DOC monotherapy (A arm; 60 mg/m2, day 1, q 3 wks) or a combination chemotherapy (B arm) of DOC (40 mg/m2, day 1, q 3 wks) and S-1 (80 mg/m2, days 1 to 15). The doses of arm B were determined based on the results of a phase I study conducted for Japanese pts with gastric cancer (Anticancer Res 24: 1843, 2004). The primary endpoint was response rate and secondary endpoints included OS, PFS and toxicity. Results: Between 2005 and 2008, 60 pts were enrolled (A/B: 29/31 pts). Demographics of the pts were as follows: M/F: 49/11, Ad/others: 40/20, ECOG-PS 0/1: 38/22. A median number of courses administered was 4 (range: 1 to 6). Objective response was obtained in 6 (20.7%) and 5 pts (16.1%) in arms A and B, respectively. With a median follow-up time of 16.9 months, MST and median PFST in arm A were longer than arm B (22.9 vs. 8.7 months and 3.7 vs. 3.4 months, respectively). The major toxicity was myelosuppression, with grade 4 neutropenia of 62% vs. 29%, whereas thrombocytopenia was generally mild. Grade 3 febrile neutropenia was observed in 4 and 1 pts, none of whom further developed grade 5 toxicity. Other grade 3 or greater non-hematological adverse events included fever (B: 1 pt), pneumonitis (B: 1 pt), liver dysfunction (B: 2 pts), skin rash (B: 1 pt), and all of them were improved with an appropriate supportive care. Conclusions: The trial suggests that docetaxel monotherapy remains a standard therapy for NSCLC pts who relapsed to platinum-based chemotherapy. No significant financial relationships to disclose.

Randomized phase II study of gemcitabine-oxaliplatin or gemcitabine-cisplatin in chemonaive patients with advanced non-small cell lung cancer (NSCLC)-CLEO 05

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7097-7097 ◽  
Author(s):  
T. Le Chevalier ◽  
S. Thezenas ◽  
J. Breton ◽  
J. Pujol ◽  
B. Coudert ◽  
...  
Keyword(s):  
Objective Response ◽  
Stage Iv ◽  
Patient Characteristics ◽  
Median Number ◽  
Stage Iiib ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
Number Of Cycles ◽  
To Receive

7097 Background: Gemcitabine-cisplatin is one of the reference doublets used in NSCLC. Oxaliplatin is a platin analog which offers a promising efficacy/tolerance profile in NSCLC. The combination of gemcitabine and oxaliplatin has been proven feasible and active in solid tumors. Methods: Patients with chemonaive, measurable, PS 0 or 1, stage IIIB/ IV NSCLC were randomized to receive either gemcitabine 1,250 mg/m2 day 1 & 8 plus oxaliplatin 130 mg/m2 day 1 (GEMOX) or gemcitabine 1,250 mg/m2 day 1 & 8 plus cisplatin 80 mg/m2day 1 (GEMCIS). Cycles were given every 3 weeks. The primary endpoint of the study was the response rate according to the RECIST criteria. Secondary endpoints included tolerance, survival and quality of life. Results: Between October 2003 and December 2004, 130 patients (66 in GEMOX and 64 in GEMCIS) were accrued at 12 centres. Baseline patient characteristics were similar in the 2 groups. Mean age was 61. There were 96 males and 34 females; 27% of patients were PS 0 and 73% were PS 1; 15% had stage IIIB and 85% had stage IV. Median number of cycles was 5 in each group. Objective response rates were 36% in GEMOX (CI 95%: 25%-50%) and 39% in GEMCIS (CI 95%: 28%-54%) respectively. Time to progression was 173 days in the GEMOX group and 163 days in the GEMCIS group. Median survival was 10.8 months in the GEMOX group and 10.4 months in the GEMCIS group. Grade III/IV neutropenia was observed in 38% of patients after GEMOX and 41% after GEMCIS; thrombocytopenia was observed in 40% and 33% of cases respectively. Grade 2+ neurotoxicity was more frequent after GEMOX (18% vs 3%). Conclusions: GEMOX has an activity comparable to GEMCIS and may be an alternative for those patients with advanced NSCLC who have a contra-indication to cisplatin. [Table: see text]

Phase II trial of sorafenib (bay 43–9006) in patients with advanced anaplastic carcinoma of the thyroid (ATC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6058-6058 ◽  
Author(s):  
G. Nagaiah ◽  
P. Fu ◽  
J. K. Wasman ◽  
M. M. Cooney ◽  
C. Mooney ◽  
...  
Keyword(s):  
Median Time ◽  
Phase Ii ◽  
Median Duration ◽  
Kinase Inhibitor ◽  
Objective Response ◽  
Median Number ◽  
Anaplastic Carcinoma ◽  
Open Label ◽  
Open Label Phase ◽  
Number Of Cycles

6058 Background: Sorafenib (bay 43–9006) is an oral, small molecule tyrosine kinase inhibitor of the raf-1 protein kinase receptor, VEGFR2 and PDGFR-β with antiangiogenic properties. We are conducting an open label, phase II study of sorafenib in patients with biopsy-proven ATC to evaluate if its objective response rate is >20% and to further characterize its safety profile. Methods: Patients with progressive ATC, after cytotoxic chemotherapy with or without radiation were given sorafenib, on a fixed dosing schedule of 400 mg PO bid on 28-day cycles. Treatment was continued until disease progression, unacceptable toxicity or patient refusal. Response was evaluated every 8 weeks with body scans using RECIST criteria. We employed a 2-stage study design: if none of the first 18 patients respond the study is terminated, otherwise accrual is continued to a total of 36 patients at which point if ≤3 of the patients respond, the treatment option is rejected. Results: To date 16 patients (10 male) have enrolled in the study. Median age is 55 years; with (range 28–79). Median time on study is 2 months. Median number of cycles given is 2 (range 1–27). Two of 15 evaluable patients (13%) have partial response (PR) and 4 patients (27%) have stable disease (SD). Median duration of PR/SD is 5.1 months (range 1–24.7months). Median time to progression is 1.5 months. Median duration of survival is 3.5 months (range 1–26 months). All patients at time of reporting are deceased. Most common toxicities are lymphopenia (81%) and fatigue (62%). Grade 3 toxicities include lymphopenia (25%), rash with desquamation, weight loss, and chest pain (all 12%). Grade 4 toxicities include dyspnea (6%) and lymphopenia (6%). There has been no significant cardiovascular toxicity. One patient died on study with rapidly progressive disease. Conclusions: Sorafenib demonstrates objective tumor response in the first 15 evaluable and pretreated patients with advanced ATC. This trial is ongoing and supported in part by NIH grant nos. CA62502. [Table: see text]

A phase II study of the anti-IGFR antibody MK-0646 in combination with cetuximab and irinotecan in the treatment of chemorefractory metastatic colorectal cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4127-4127
Author(s):  
D. J. Watkins ◽  
J. Tabernero ◽  
H. J. Schmoll ◽  
T. Trarbach ◽  
F. J. Ramos ◽  
...  
Keyword(s):  
Phase Ii ◽  
Drug Combination ◽  
Phase Ii Study ◽  
Study Drug ◽  
Skin Toxicity ◽  
Median Number ◽  
Tissue Samples ◽  
Radiological Response ◽  
Number Of Cycles ◽  
To Receive

4127 Background: Evidence of cross-talk between EGFR and IGFR signaling pathways provide a logical rationale for combining anti-EGFR and anti-IGFR strategies in the treatment of cancer. Prior to commencing a blinded randomised phase II study, an opened-labelled safety run-in was undertaken to assess the tolerability of a three-drug combination utilizing irinotecan (Ir), cetuximab (Cx) and two schedules of MK-0646 (Mk). Methods: Eligible patients (pts) had previously failed both Ir and oxaliplatin and had progressed on or within 3 months of their last therapy. Pts were required to have measurable disease and tissue samples available for tumour KRAS testing. Pts were randomised to receive either Mk 10mg/kg weekly (Arm A) or Mk 15mg/kg loading followed by 7.5mg/kg every alternate week (Arm B). All randomised pts also received Cx 400mg/m2 loading followed by 250mg/m2 weekly and Ir according to the same dose and schedule as they had previously received. Patients continued on treatment until disease progression with radiological response assessments undertaken every 6 weeks. Results: 10 pts were recruited to Arm A and 8 to Arm B. Pt characteristics: median age 60.5 years, male 67%, PS 0/1 33%/67%. Median number of prior chemotherapy regimens 3. The median number of cycles of Mk received in Arm A and B is 25 and 8 respectively. Reported grade III/IV toxicities in Arm A and Arm B were: neutropenia 30% and 0%, diarrhoea 30% and 25%, hypomagnesemia 0% and 25%. Hyperglycemia (≥ grade 2) was seen in 10% of Arm A and 25% in Arm B. Acneiform skin toxicity (≥ grade 2) was seen in 30% of Arm A and 62% of Arm B. The radiological response rate was 33% in Arm A and 14% in Arm B. The median time on study drug is 5.8 months in Arm A and 3.9 months in Arm B. 2 pts on Arm A and 1 in Arm B remain on study therapy. Tumour KRAS testing is in progress. Conclusions: The combination of MK-0646, cetuximab and irinotecan is tolerable with no concerning overlapping toxicities highlighted. PFS and KRAS data will be available for presentation. The efficacy of this three drug combination is under evaluation in an ongoing randomised phase II/III study. [Table: see text]

Rechallenge with trabectedin in patients with locally advanced or metastatic soft tissue sarcoma following drug holiday: The experience of the French Sarcoma Group (FSG).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10062-10062 ◽  
Author(s):  
Esma Saada ◽  
Chahineze Rahal ◽  
Isabelle Ray Coquard ◽  
Antoine Italiano ◽  
Christine Chevreau ◽  
...  
Keyword(s):  
Soft Tissue ◽  
Objective Response ◽  
Locally Advanced ◽  
Soft Tissue Sarcomas ◽  
Myxoid Liposarcoma ◽  
Median Number ◽  
Drug Holiday ◽  
Who Grade ◽  
Well Differentiated ◽  
Number Of Cycles

10062 Background: Trabectedin (T) is a marine-derived alkaloid used to treat advanced soft tissue sarcomas (STS) after ifosfamide and/or anthracyclins failure. Since then, the FSG evaluated the clinical benefit in re-administrating T after an initial hold, either medically indicated or upon patient’s request. Methods: Following an online request, clinical and histopathological data were collected from six centers of the FSG who declared to have rechallenged patients. Baseline data were collected and analyze will be used. Results: From 1999 to 2011, 49 pts with T drug holiday have been identified (26 male/ 23 female), with a median age of 50 y [23-75]. Most frequent histotypes were: myxoid liposarcoma (18, 36.7%), leiomyosarcomas (13, 26.5 %) and well-differentiated/dedifferentiated liposarcoma (9, 18%). WHO grade were 1 in 14 (29%), 2 in 19 (39%) and 3 in 5 (10%) pts respectively. Patients who had a maximum of 2, 3 or 4 therapeutic sequences (TS) with T (drug-holiday and rechallenge) were 41/49 ,7/49 and 1/49 respectively. Median number of cycles for 1, 2, 3 and 4 TS were 7 [3-21], 6 [2-30], 6 [2-9] and 6. Median total number of cycles was 15 [6-43]. Median duration of drug-holiday for 1, 2 and 3 TS were 11 [3-91], 7 [2-29] and 4 months [1-5]. Grade 3-4 toxicities incidence decreased with the number of TS (occurred in 36%, 29%, 14% and 0% of pts with 1, 2, 3 and 4 TS) as well as mean T dose per cycle (1.3 mg/m², 1.2 mg/m², 1.1 mg/m² and 1.1 mg/m² for TS 1, 2, 3, 4). Efficacy decreased with number of TS (Number of CR/PR/SD/PD were 1 (2%)/15 (31%)/33 (67%)/0 for TS1; 0/4 (8%)/29 (59%)/16 (3%) for TS2; 0/1 (14%)/2 (29%)/4 (57%) for TS3 and 0/0/0/1(100%) for TS4). Median overall survival was 5.0 y [2.7-7.3] since T introduction, and 1.5 y [0.1-4.8], 0.8 y [0.5-1.3] and 0.6 y following 2nd, 3rd and 4th T reintroduction respectively. Objective response after TS2 were seen in 4 cases of grade 1 sarcomas. Conclusions: Due to the lack of cumulative toxicities over time with T, its rechallenging in responding patients to T (no progression under T) have to be considered in advanced STS.

SPIRITT (study 20060141): A randomized phase II study of FOLFIRI with either panitumumab (pmab) or bevacizumab (bev) as second-line treatment (tx) in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 454-454 ◽  
Author(s):  
J. Randolph Hecht ◽  
Allen Lee Cohn ◽  
Shaker R. Dakhil ◽  
Mansoor N. Saleh ◽  
Bilal Piperdi ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Eligibility Criteria ◽  
Grade 5 ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
Previously Treated

454 Background: Pmab has demonstrated significant improvement in progression-free survival (PFS) in pts with WT KRAS mCRC as 2nd-line tx in a phase III trial comparing pmab + FOLFIRI vs FOLFIRI alone. Here, we describe the results of SPIRITT, a multicenter, randomized phase II study evaluating pmab + FOLFIRI and bev + FOLFIRI in pts with WT KRAS mCRC previously treated with a 1st-line bev + oxaliplatin (Ox)-based chemotherapy regimen. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg + FOLFIRI Q2W or to bev 5.0 or 10.0 mg/kg + FOLFIRI Q2W. Eligibility criteria included: WT KRAS mCRC, ECOG ≤ 1, no prior irinotecan or anti-EGFR tx, and tx failure of prior 1st-line bev + Ox-based therapy (≥ 4 cycles). The primary endpoint was PFS; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. No formal hypothesis was tested. Results: 182 pts with WT KRAS mCRC were randomized. All pts received tx. Efficacy results are shown (table). Worst grade of 3/4 adverse events (AE) occurred in 78% of pts in the pmab + FOLFIRI arm and 65% in the bev + FOLFIRI arm. Grade 5 AEs occurred in 7% of pts in the pmab + FOLFIRI arm and 7% in the bev + FOLFIRI arm. Tx discontinuation due to any AE was 29% in the pmab + FOLFIRI arm and 25% in the bev + FOLFIRI arm. Conclusions: In this estimation study of pts with WT KRAS mCRC that previously received bev + Ox-based tx, the PFS hazard ratio (HR) was 1.01 (95% CI: 0.68 - 1.50). The OS HR was 1.06 (95% CI: 0.75 - 1.49). The observed ORR was higher in the pmab + FOLFIRI arm. 54% of bev + FOLFIRI pts received subsequent anti-EGFR tx. The safety profile for both arms was similar to previously reported studies. Tx discontinuation rates due to AEs were similar between the arms. Clinical trial information: NCT00418938. [Table: see text]

Cisplatin in Combination With Either Gemcitabine or Irinotecan in Carcinomas of Unknown Primary Site: Results of a Randomized Phase II Study—Trial for the French Study Group on Carcinomas of Unknown Primary (GEFCAPI 01)

2003 ◽  
Vol 21 (18) ◽  
pp. 3479-3482 ◽  
Author(s):  
Stéphane Culine ◽  
Alain Lortholary ◽  
Jean-Jacques Voigt ◽  
Roland Bugat ◽  
Christine Théodore ◽  
...  
Keyword(s):  
Phase Ii Study ◽  
Median Number ◽  
Primary Site ◽  
Unknown Primary ◽  
Unknown Primary Site ◽  
Randomized Phase Ii ◽  
French Study ◽  
Number Of Cycles ◽  
To Receive

Purpose: To evaluate the efficacy and toxicity of novel chemotherapy combinations including cisplatin with gemcitabine (GC) or irinotecan (IC) for patients with carcinomas of an unknown primary site. Patients and Methods: Eighty patients were randomly assigned to receive GC or IC. In the GC arm, chemotherapy consisted of cycles combining gemcitabine 1,250 mg/m2 intravenously (IV) on days 1 and 8, and cisplatin 100 mg/m2 IV on day 1 at 3-week intervals. Patients in the IC arm originally received 3-week cycles of irinotecan 200 mg/m2 IV on day 1 and cisplatin 80 mg/m2 IV on day 1. After the inclusion of 15 patients in that arm, the toxicity profile required the irinotecan doses to be reduced to 150 mg/m2 per cycle. Independent histologic and radiologic reviews were done. Results: A total of 78 patients were assessable for efficacy and toxicity. The median number of cycles was four in each arm. Objective responses were observed in 21 patients (55%) in the GC arm (95% CI, 34% to 66%) and in 15 patients (38%) in the IC arm (95% CI, 23% to 54%). Treatment had to be stopped because of toxicity in seven patients in the GC arm and in eight patients in the IC arm. With a median follow-up of 22 months, the median survivals were 8 and 6 months in the GC and IC arms, respectively. Conclusion: This study demonstrates the activity of both the GC and IC regimens. There was toxicity associated with both regimens. Additional studies of combination chemotherapy regimens are required.

Paclitaxel plus carboplatin in advanced carcinoma of the urothelium: an active and tolerable outpatient regimen.

1998 ◽  
Vol 16 (1) ◽  
pp. 255-260 ◽  
Author(s):  
D J Vaughn ◽  
S B Malkowicz ◽  
B Zoltick ◽  
R Mick ◽  
P Ramchandani ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Objective Response ◽  
Median Number ◽  
Maximum Tolerated Dose ◽  
Time Curve ◽  
Creatinine Concentration ◽  
Advanced Carcinoma ◽  
Median Serum ◽  
Number Of Cycles

PURPOSE To determine the toxicity and efficacy of an outpatient regimen of paclitaxel plus carboplatin in patients with advanced carcinoma of the urothelium. PATIENTS AND METHODS Patients received paclitaxel 150 to 225 mg/m2 over 3 hours followed by carboplatin (targeted area under the concentration-time curve [AUC], 6 mg/mL x min) every 3 weeks. During phase I accrual, 16 patients were treated; 17 additional patients were enrolled at the phase II dose. The median age was 70 years (range, 47 to 82). The median serum creatinine concentration was 1.1 mg/dL (range, 0.7 to 2.7) and the median estimated creatinine clearance was 52 mL/min (range, 24 to 110). RESULTS During phase I accrual, the maximum-tolerated dose (MTD) of the regimen was not defined. Phase II accrual occurred at the paclitaxel 225 mg/m2 dose level. A total of 156 cycles were administered. The median number of cycles received was five (range, one to eight). Sensorimotor neuropathy was the principal nonhematologic toxicity. Significant granulocytopenia was common, but significant thrombocytopenia was not. Objective responses were demonstrated at all dose levels. At the phase II dose (paclitaxel 225 mg/m2 followed by carboplatin at AUC 6 mg/mL x min), the objective response rate was 50% (95% confidence interval [CI], 28% to 72%). CONCLUSION Paclitaxel plus carboplatin is an active and tolerable outpatient treatment for patients with advanced carcinoma of the urothelium. The ability to administer this combination over multiple cycles even to patients with advanced age and abnormal renal function makes it well suited for this patient population. Confirmatory trials of this regimen are ongoing.

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