Eastern Cooperative Oncology Group Phase I Trial of Protracted Venous Infusion Fluorouracil Plus Weekly Gemcitabine With Concurrent Radiation Therapy in Patients With Locally Advanced Pancreas Cancer: A Regimen With Unexpected Early Toxicity

2000 ◽  
Vol 18 (19) ◽  
pp. 3384-3389 ◽  
Author(s):  
Mark S. Talamonti ◽  
Paul J. Catalano ◽  
David J. Vaughn ◽  
Richard Whittington ◽  
R. Daniel Beauchamp ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Phase I ◽  
Dose Level ◽  
Phase I Trial ◽  
Pancreas Cancer ◽  
Locally Advanced ◽  
Stevens Johnson Syndrome ◽  
Severe Bleeding ◽  
Severe Thrombocytopenia ◽  
Venous Infusion

PURPOSE: We performed a phase I trial of protracted venous infusion (PVI) fluorouracil (5-FU) plus weekly gemcitabine with concurrent radiation therapy in patients with locally advanced pancreas cancer to determine the maximum-tolerated dose of gemcitabine that could be safely administered. We also sought to identify the toxicities associated with this treatment protocol. PATIENTS AND METHODS: Seven patients with locally advanced pancreas cancer were treated with planned doses of radiation (59.4 Gy) and PVI of 5-FU (200 mg/m2/d) with gemcitabine doses of 50 to 100 mg/m2/wk. RESULTS: Two of three patients at the 100-mg/m2/wk dose level experienced dose-limiting toxicity (DLT), as did three of four at the 50-mg/m2/wk dose level. One patient experienced a mucocutaneous reaction described as a Stevens-Johnson syndrome that was attributed to chemotherapy. Three patients developed gastric or duodenal ulcers with severe bleeding requiring transfusion. One patient developed severe thrombocytopenia lasting longer than 4 weeks. Three of the five episodes of DLT developed at radiation doses ≤ 36 Gy. CONCLUSION: Based on this experience, we cannot recommend further investigation of regimens incorporating gemcitabine into regimens of radiation with PVI 5-FU. The mechanism of this synergistic toxicity remains to be determined.

Concurrent treatment with everolimus (RAD001) and hormonoradiotherapy in high-risk locally advanced prostate cancer: Results of a phase I trial.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 150-150 ◽  
Author(s):  
David Azria ◽  
Xavier Rebillard ◽  
Nathalie Coux ◽  
Marta Jarlier ◽  
Rodolphe Thuret ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Phase I ◽  
Dose Level ◽  
Advanced Prostate Cancer ◽  
Phase I Trial ◽  
Locally Advanced ◽  
Locally Advanced Prostate Cancer ◽  
Grade 3 ◽  
Dose Levels

150 Background: Everolimus is able to stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Giving everolimus together with hormonotherapy and radiation therapy may kill more tumor cells. Methods: We conducted a phase I trial to evaluate the impact of everolimus (RAD001), an mTOR inhibitor, in patients treated concurrently with radiotherapy (RT) and ablative androgen treatment in high-risk locally advanced prostate cancer. Inclusion criteria were high-risk locally advanced non metastatic prostate cancer defined as clinical stage ≥ T3 or Gleason score ≥ 8 or PSA ≥ 20. The week before the beginning of RT, RAD001 was administered at different dose levels, twice daily, until the last day of irradiation. A nonsteroid antiandrogen was also given for 1 month at the beginning of RT. Prostate and seminal vesicle were irradiated up to 74Gy in 37 fractions of 2Gy with concomitant long-term LHRH analogue. The starting dose of RAD001 was 5mg/d with subsequent dose levels of 7.5 and 10 mg/d. The primary endpoint was the determination of the maximum tolerated dose (MTD). Dose escalation was implemented according to the continual reassessment method (CRM). Results: Fifteen patients were enrolled and 14 were assessable for toxicity and response. Significant toxicities were demonstrated at the 7.5 and 10 mg/d dose levels. Dose-limiting toxicity (DLT) occurred in two patients at dose level 7.5 mg/d and characterized by a grade 3 diarrhea and a grade 3 hydronephrosis due to dehydration and kidney lithiasis. DLT also occurred in two patients at dose level 10 mg/d (grade 3 diarrhea and grade 3 laryngopharyngeal infection). The MTD was reached at 7.5 mg/day (dose-level II). The recommended dose of RAD001 was 5 mg/d. After a median follow-up of 22 months, 12 patients are alive, 1 is dead (not related to cancer) and 2 patients had relapsed. Conclusions: Concomitant hormone-radiotherapy and everolimus is well-tolerated with mucositis, hypercholesterolemia, and urinary disorders. The recommended phase-II trial dose of everolimus in this combined setting is 5 mg/day. Clinical trial information: NCT00943956.

A phase I study of erlotinib, bevacizumab, and external beam radiation therapy (RT) for patients with localized pancreatic carcinoma (PC).

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 281-281 ◽  
Author(s):  
B. G. Czito ◽  
C. Willett ◽  
P. Kennedy-Newton ◽  
D. S. Tyler ◽  
H. Hurwitz ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Phase I ◽  
Dose Level ◽  
Phase Ii ◽  
Phase I Study ◽  
Locally Advanced ◽  
Exploratory Laparotomy ◽  
External Beam Radiation ◽  
Beam Radiation ◽  
Level 1

281 Background: Localized PC is commonly managed with chemoradiotherapy, with or without surgical resection. The optimal combination of agents and doses is the subject of continued investigation. This phase I study examines the combination of two targeted radiosensitizing agents in combination with radiation therapy. Methods: Eligible patients had resectable, borderline resectable or locally advanced adenocarcinoma. Patients received RT (1.8 Gy qd to 50.4 Gy) concurrent with bevacizumab and erlotinib. Dose-level 1 was bevacizumab 10 mg/kg weeks 1, 3 and 5 and erlotinib 100 mg daily, RT days only. Drug doses were escalated depending on encountered toxicity. The primary endpoint was determination of the maximally tolerated dose of this combination. Secondary endpoints included toxicity and activity assessment. Results: Nine patients were enrolled in the phase I study. Maximal EUS/CT stage was T2N0 (n=1), T3N0 (n=1), T3N1 (n=2) or T4N0 (n=5). Of 3 patients in dose-level 1, two had radiographic stable disease (SD) and one partial response (PR). One pt underwent exploratory laparotomy and found to be unresectable, experiencing prolonged postoperative incisional healing. Three patients were then enrolled at dose-level 2 (bevacizumab 10 mg/kg, erlotinib 125 mg). Two had SD and one progressive disease (PD). One pt underwent exploratory laparotomy, aborted due to previously undetected hepatic metastases. Three patients were then enrolled at dose-level 3 (bevacizumab 10 mg/kg, erlotinib 150 mg). One pt had SD and two PR. One pt underwent distal pancreatectomy, experiencing postoperative pancreatic leak and abscess formation. All patients with elevated CA 19-9 at baseline had a decrease, with amedian decrease of 69% (R:13-93%). Dose-limiting toxicity (DLT) was not encountered at any dose-level. Primary non-dose limiting toxicities in all cohorts included NCI CTCAE v3.0 grade 1-2 nausea/vomiting, rash, diarrhea, fatigue, and anorexia. Conclusions: Concurrent chemoradiotherapy utilizing erlotinib and bevacizumab is reasonably well-tolerated. The recommended phase II dose is bevacizumab 10 mg/kg weeks 1, 3, and 5 and erlotinib 150 mg RT days only. Phase II accrual is underway. [Table: see text]

Phase I Trial of Weekly Docetaxel With Concurrent Three-Dimensional Conformal Radiation Therapy in the Treatment of Unfavorable Localized Adenocarcinoma of the Prostate

2004 ◽  
Vol 22 (10) ◽  
pp. 1909-1915 ◽  
Author(s):  
Parvesh Kumar ◽  
Michael Perrotti ◽  
Robert Weiss ◽  
Mary Todd ◽  
Susan Goodin ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
Phase I ◽  
Dose Level ◽  
Phase I Trial ◽  
Specific Antigen ◽  
Three Dimensional ◽  
Conformal Radiation Therapy ◽  
Weekly Docetaxel ◽  
Adenocarcinoma Of The Prostate ◽  
Grade 3

Purpose A phase I trial was conducted to determine the maximally tolerated dose (MTD) of concurrent weekly docetaxel and three-dimensional conformal radiation therapy (3-D CRT) in unfavorable localized adenocarcinoma of the prostate. Patients and Methods Patients with unfavorable localized adenocarcinoma of the prostate underwent daily 3-D CRT to a total dose of 70.2 Gy at 1.8 Gy/fraction and concurrent docetaxel given once a week for 8 to 9 weeks. The initial weekly docetaxel dose level was 5 mg/m2 and the docetaxel doses were escalated as follows: 8, 12, 16, 20, and 25 mg/m2. Results Between January 2000 and August 2002, 22 men completed the chemoradiation therapy protocol. The dose-limiting toxicity was grade 3 diarrhea, which occurred in the first two patients treated at the 25 mg/m2 docetaxel dose level. The MTD of weekly docetaxel was determined to be 20 mg/m2. The overall incidence of grade 2 diarrhea and grade 2 dysuria was 36% and 23%, respectively. Seven (32%) and 15 (68%) patients did not experience any diarrhea or dysuria, respectively. No neutropenia or thrombocytopenia was observed. One patient required intermittent urinary catherization 10 months postcompletion of therapy, which resolved without any surgical intervention. Seventeen patients remain in prostate-specific antigen remission. At a median follow-up interval of 8 months (range, 2 to 27 months), all patients are alive. Conclusion Concurrent weekly docetaxel in conjunction with 3-D CRT is well tolerated with acceptable toxicity. The MTD of weekly docetaxel was determined to be 20 mg/m2 with concurrent 3-D CRT.

Phase I trial of docetaxel, oxaliplatin and capecitabine (TEX) in patients with metastatic gastric cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14051-14051 ◽  
Author(s):  
W. Grothe ◽  
R. D. Hofheinz ◽  
L. Mantovani Loeffler ◽  
J. Böhme ◽  
D. Arnold ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Phase I ◽  
Dose Level ◽  
Phase I Trial ◽  
Locally Advanced ◽  
Metastatic Gastric Cancer ◽  
Maximum Tolerated Dose ◽  
Primary Tumor Site ◽  
Level 1 ◽  
Ecog Ps

14051 Background: Combination regimens of 3 active drugs have shown promising activity in treatment of metastatic gastric cancer (GC). Docetaxel (D) combined with cisplatin and 5-FU (CF) yielded superior overall survival and response rates when compared to standard CF. However, toxicity profile showed the need for development of less toxic modifications. In this phase I trial, D was combined with oxaliplatin (Ox) and capecitabine (Cape) in order to define the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) in patients (pts) with metastatic GC. Methods: Pts had to have metastatic or locally advanced GC, adequate organ function, ECOG PS 0–2, no prior chemotherapy. Four dose levels were planned planned for the TEX regimen: D 35–40 mg/m2, Ox 70 mg/m2 d1 and d88, with Cape 800–1000 mg/m2 bid d1–14 q d22. Toxicity was assessed 3-weekly whereas CT scans were repeated 9-weekly. Results: 14 pts were enrolled: 9m/5f, age 64 (42–76) yrs, ECOG PS 1 [0–2]. All pts. had distant metastatis, 10 no gastrectomy. On dose level 1 (D 35 mg/m2, Ox 70 mg/m2, Cape 800 mg/m2) 3 pts were included initially. 1 pt. had grade 4 bleeding from primary tumor site after 2nd administration and therefore was excluded. For safety reasons, 6 more pts. were enrolled - without further DLT. On dose level 2 (D 40 mg/m2, Ox 70 mg/m2, Cape 800 mg/m2), diarrhea and mucositis grade 3 occurred as DLT in 2/2 patients. Level 1 was determined as MTD and 5 more pts were included to a total of 12 with toxicity displayed at the table. Out of 10 pts with measurable disease, 3 had a PR, 4 more had disease stabilization. Median PFS of all pts (5 censored) is 3.9+ (1–9.3+) mos. whereas median OS is not yet reached. Conclusion: TEX can safely be administered without higher graded toxicity in pts with GC. Preliminary efficacy results indicate promising activity that merits further testing in a phase II trial. [Table: see text] [Table: see text]

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