Phase I study of recombinant leukocyte A human interferon combined with BCNU in selected patients with advanced cancer.

Interferons manifest diverse immunomodulatory and antiproliferative characteristics. Since their spectrum of toxicities includes primarily fatigue and anorexia rather than the myelosuppression concomitant with cytotoxic therapies, it is conceptually appealing to combine both modalities. We conducted a phase I trial among 18 patients using the combination of leukocyte A recombinant interferon (IFN-rA) and BCNU. The intramuscular (IM) IFN-rA dose for the initial 12 patients was 12 X 10(6) U/m2 three times a week for an anticipated duration of 12 weeks. Among these patients, we escalated the monthly intravenous (IV) BCNU dose from 50 mg/m2 to 150 mg/m2. Six subsequent patients received IFN-rA 12 X 10(6) U/m2, days 1 to 3, and BCNU 150 mg IV on day 3 of each monthly cycle. Dose-limiting toxicities from both regimens were fatigue and myelosuppression. We recognize the limitation of small sample sizes. Nevertheless, in the absence of a significant number of life-threatening toxicities, it appears that near maximal doses of BCNU and concomitant IFN-rA can be administered with safety in an outpatient setting.

Download Full-text

Phase I trial of continuous infusion carboplatin and etoposide in children with refractory acute leukemia: a Pediatric Oncology Group study.

Journal of Clinical Oncology ◽

10.1200/jco.1994.12.9.1969 ◽

1994 ◽

Vol 12 (9) ◽

pp. 1969-1973 ◽

Cited By ~ 3

Author(s):

P D Sadowitz ◽

R Dubowy ◽

A Souid ◽

B H Pollock ◽

H Weinstein ◽

...

Keyword(s):

Acute Leukemia ◽

Phase I ◽

Continuous Infusion ◽

Phase I Study ◽

Phase I Trial ◽

Phase Ii Trial ◽

Fixed Dose ◽

Life Threatening ◽

Pediatric Oncology Group ◽

Grade Iii

PURPOSE The purpose of this phase I study was to determine the toxicities and response to continuous infusion carboplatin in combination with a fixed dose of etoposide (VP-16) in children with refractory acute leukemia. PATIENTS AND METHODS From January 1989 to February 1992, 20 patients received 28 courses of treatment. Each course of treatment consisted of a 1-hour intravenous (IV) infusion of VP-16 100 mg/m2/d for 5 days, followed by a 23-hour IV infusion of carboplatin each day. The initial, total 5-day dose of carboplatin (1,000 mg/m2) was escalated by 250- to 375-mg increments to a final, total dose of 1,875 mg/m2 over 5 days. RESULTS Significant marrow suppression was observed in all patients, with prolonged marrow aplasia at the 1,875-mg/m2 dose level. Grade III diarrhea occurred in three patients; 10 patients experienced life-threatening infection and three had severe thrombocytopenic bleeding. Major marrow responses (two complete remissions and two partial remissions) occurred in four patients (20%). CONCLUSION In view of the apparent antileukemic efficacy and minimal extramedullary toxicity, carboplatin deserves further study in a phase II trial.

Download Full-text

Phase I trial of concurrent intraperitoneal and continuous intravenous infusion of fluorouracil in patients with refractory cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1988.6.1.158 ◽

1988 ◽

Vol 6 (1) ◽

pp. 158-162 ◽

Cited By ~ 10

Author(s):

B Reichman ◽

M Markman ◽

T Hakes ◽

N Kemeny ◽

D Kelsen ◽

...

Keyword(s):

Phase I ◽

Intravenous Infusion ◽

Phase I Study ◽

Clinical Utility ◽

Phase I Trial ◽

Drug Exposure ◽

Continuous Intravenous Infusion ◽

Future Studies ◽

Systemic Drug Exposure ◽

Systemic Drug

In an effort to maximize both local-regional and systemic drug exposure to tumor in the peritoneal cavity, a phase I study was conducted that examined the simultaneous daily intraperitoneal (IP) and continuous intravenous infusion (CVI) of fluorouracil (5-FU) to 32 patients with refractory cancer. IP 5-FU administered at 1,000 mg/d with concurrent 5-FU by CVI at 1,000 mg/m2/d for four consecutive days was well tolerated. One patient with a primary gastrointestinal (GI) malignancy with minimal volume disease experienced a surgically defined complete remission. In theory, this regimen may demonstrate clinical utility as an adjuvant treatment of certain GI malignancies. Future studies are planned in this clinical setting.

Download Full-text

Clinical and Biological Effects of Recombinant Interferon-β Administered Intravenously Daily in Phase I Trial

Journal of Interferon Research ◽

10.1089/jir.1988.8.357 ◽

1988 ◽

Vol 8 (3) ◽

pp. 357-366 ◽

Cited By ~ 22

Author(s):

ERNEST C. BORDEN ◽

MICHAEL J. HAWKINS ◽

KAREN M. SIELAFF ◽

BARRY M. STORER ◽

JUDE D. SCHIESEL ◽

...

Keyword(s):

Phase I ◽

Phase I Trial ◽

Biological Effects ◽

Interferon Β ◽

Recombinant Interferon

Download Full-text

Facilitating Resolution of Life-Threatening Acute Graft-Versus-Host Disease By Supplementation of Human Chorionic Gonadotropin and Epidermal Growth Factor (Pregnyl®): A Phase I Study

Biology of Blood and Marrow Transplantation ◽

10.1016/j.bbmt.2018.12.236 ◽

2019 ◽

Vol 25 (3) ◽

pp. S240-S241 ◽

Cited By ~ 1

Author(s):

Shernan G. Holtan ◽

Andrea Hoeschen ◽

Qing Cao ◽

Mukta Arora ◽

Veronika Bachanova ◽

...

Keyword(s):

Growth Factor ◽

Epidermal Growth Factor ◽

Phase I ◽

Chorionic Gonadotropin ◽

Graft Versus Host Disease ◽

Phase I Study ◽

Graft Versus Host ◽

Life Threatening ◽

Epidermal Growth ◽

Acute Graft

Download Full-text

A combination phase I study of weekly paclitaxel and 5'-DFUR in patients with unresectable or recurrent gastric cancer in an outpatient setting

Journal of Clinical Oncology ◽

10.1200/jco.2004.22.14_suppl.4228 ◽

2004 ◽

Vol 22 (14_suppl) ◽

pp. 4228-4228 ◽

Cited By ~ 1

Author(s):

S. Yoshino ◽

M. Oka ◽

S. Hazama ◽

K. Hamano ◽

H. Hayashi ◽

...

Keyword(s):

Gastric Cancer ◽

Phase I ◽

Phase I Study ◽

Outpatient Setting ◽

Weekly Paclitaxel ◽

Recurrent Gastric Cancer

Download Full-text

Phase I trial of bortezomib in combination with topotecan in advanced solid tumor malignancies

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.12004 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 12004-12004

Author(s):

R. Morgan ◽

F. Valdes-Albini ◽

T. Synold ◽

G. Somlo ◽

S. Shibata ◽

...

Keyword(s):

Phase I ◽

Phase I Study ◽

Phase I Trial ◽

Hematologic Toxicity ◽

Weekly Schedule ◽

Clinical Testing ◽

Advanced Solid Tumor ◽

Advanced Malignancies ◽

Grade 3 ◽

Tumor Types

12004 Background: Bortezomib (B) and topotecan (T) have been shown in pre-clinical testing to be synergistic. Based on this data we have performed a phase I study to determine the maximally tolerated dose and toxicities (tox) of B and T delivered sequentially. Methods: 24 pts (KPS<ECOG 3) with advanced malignancies were treated with T (2.0, 2.5, 3.0 or 3.5 mg/m2 in sequential cohorts) IV on days 1 and 8 of each three week cycle. B 1.3 mg/m2 iv was administered six hours following T on days 1 and 8, and alone on days 4 and 12. Pts were treated in cohorts of 3, the MTD dose was expanded to include 10 additional pts for PK analysis. There was no limit on prior therapies. DLT was defined as any gr 3 or 4 non-hematologic toxicity not reversible in 48h or any gr 3 thrombocytopenia lasting >7 days or associated with bleeding or any gr 4. Results: Tumor types included: breast (4), ovary (5), lung (3), others (12). 24 pts were entered (11M 13F). The median age was 55 (range: 34–83). DLT was thrombocytopenia, observed in two pts at 3.5 mg/m2 and one pt at 3.0 mg/m2 (MTD). Other grade 3 or 4 tox included fatigue, lymphopenia, hypomagnesemia, and hypertriglyceridemia. Of the 24 enrolled pts, stable disease was observed in 4 (4 or 5 cycles), 9 progressed, 5 were inevaluable and 6 are too early. PK analysis is pending. Conclusions: T and B delivered sequentially are well tolerated on a weekly schedule. DLT is thrombocytopenia. PK will be presented.(Supported by NCI Grant CA33572). [Table: see text]

Download Full-text

A phase I study of nab-paclitaxel (A), gemcitabine (GEM), and capecitabine (X) in patients with metastatic pancreatic adenocarcinoma (MPA).

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.4048 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 4048-4048

Author(s):

Thach-Giao Truong ◽

Margaret A. Tempero ◽

Emily Kantoff ◽

Kimberly Jones ◽

Elizabeth Dito ◽

...

Keyword(s):

Phase I ◽

Dose Level ◽

Phase I Study ◽

Small Sample Size ◽

Dose Intensity ◽

Primary Objective ◽

Small Sample ◽

Study Cohort ◽

Entire Study ◽

Study Results

4048 Background: GEM-based doublets, such as GEM + capecitabine (X), may be beneficial in select pts with MPA. Given preclinical evidence of synergy when a taxane is added to GEM + X, as well as recent phase I/II study results showing substantial activity with GEM + nab-paclitaxel (A) (ORR of 48%, median OS > 12 mos at MTD), we conducted a phase I study evaluating the 3-drug combination of A, GEM, and X (AGX) given biweekly in pts with MPA. Methods: Pts with previously untreated MPA and ECOG PS 0-1 were eligible. A (100-150 mg/m2) and GEM (750-1000 mg/m2 at 10 mg/m2/min) were both administered on day 4, and X (500-1000 mg/m2 bid) on days 1-7, of each 14-day cycle. A 3+3 dose escalation design was used, with expanded cohort at MTD. Primary objective was to establish MTD of this regimen; secondary objectives include safety and preliminary assessment of efficacy. DLT definitions: gr 3-4 ANC or neutropenic fever; gr 4 plts; gr 2-4 hand-foot syndrome (HFS), neuropathy or diarrhea; or other gr 3-4 non-heme toxicity. Results: Fifteen patients were enrolled across two dose levels (age range, 45-74 y). Final MTD was established at dose level 0, consisting of A 100 mg/m2, GEM 750 mg/m2, and X 750 mg/m2 bid. At dose level 1, two of 4 pts experienced DLTs (gr 3 LFT elevation, gr 3 ANC). For the entire study cohort, 10 pts (67%) experienced at least one gr 3-4 AE, including LFTs (20%), N/V (13%), and fatigue (7%). Gr 3-4 heme toxicity was uncommon. Other notable AEs (any grade): fatigue (87%), rash/HFS (67%), N/V (53%), diarrhea (40%), neuropathy (33%). Median # cycles received = 4 (range, 2-16). 73% of pts d/c’ed study treatment due to disease progression. Best response for the entire cohort (n=14 evaluable pts): 2 PR, 8 SD, 4 PD (disease control rate = 71%). Of 12 pts with elevated CA19-9 at baseline, 5 (42%) had >50% biomarker decline. Conclusions: Recognizing the limits of cross-study comparisons and small sample size, these results do not match those reported at MTD in the phase I/II trial of GEM (1000 mg/m2) + A (125 mg/m2). The modest activity seen with this AGX regimen may have resulted from suboptimal dosing, and suggests that dose intensity may be an important factor when trying to incorporate nab-paclitaxel into multidrug regimens.

Download Full-text