Phase I/II trial of doranidazole (PR-350) and concurrent thoracic radiotherapy (TRT) in patients (pts) with locally advanced (LA) non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 17064-17064
Author(s):  
K. Takeda ◽  
S. Negoro ◽  
K. Nakagawa ◽  
Y. Segawa ◽  
Y. Nishimura ◽  
...  
Keyword(s):  
Phase I ◽  
Induction Chemotherapy ◽  
Performance Status ◽  
Locally Advanced ◽  
Cumulative Effect ◽  
Hypoxic Cell ◽  
Severe Toxicity ◽  
Ecog Performance Status ◽  
Prior Therapy ◽  
The Times

17064 Background: PR-350 was a nitoroimidazole derivative as a hypoxic cell radiosensitizer with low toxixity, developed by POLA Chemical Industries Inc.(Yokohama, Japan). We undertook this phase I/II trial to characterize the safety, pharmacokinetics (PK), and antitumor activity of the combination chemotherapy of platinum agent and paclitaxel followed by PR-350 and concurrent TRT in pts with LANSCLC. This trial was conducted by West Japan Thoracic Oncology Group (WJTOG). Methods: Major eligibility included 20–74 years old, histologically or cytologically proven NSCLC, surgically unresectable stage IIIA and IIIB, no prior therapy, ECOG performance status of 0 to 1, and adequate organ functions. All pts received two cycles of cisplatin of 80 mg/m2 and paclitaxel of 180 mg/m2 before radiotherapy with PR-350. The radiation dose was 60 Gy in 30 fractions of 2 Gy over 6 weeks. PR-350 dose of 2000 mg/m2 was administered as a 25 minutes intravenously prior to irradiation daily. The starting consecutive days were 10 times with daily TRT, and the times were escalated in increments of 10 times for successive groups of 6 new pts. PK studies of PR-350 were performed on the first day and the end. Induction chemotherapy of carboplatin (AUC = 6) and paclitaxel (200mg/m2) was also permitted in phase II portion. Results: 37 pts were enrolled into this trial. Major severe toxicity was radiation pneumonitis, which developed 2 treatment related deaths (TRD). Grade 3 or more esophagitis was not developed in this trial. PR-350 was able to administered 30 consecutive days with concurrent TRT. Overall response rate was 67.6% (95% CI: 50.2–82.0%). Median survival time was 16.8 months (95% CI: 12.1–21.9 months), and 1 and 2 year survival rate were 64% and 21%, respectively. No cumulative effect was demonstrated among 3 dose levels by PK studies. Conclusions: Induction chemotherapy followed by TRT with 30 times of PR-350 was well tolerated and promising for the treatment of LANSCLC. [Table: see text] No significant financial relationships to disclose.

Phase I/II clinical trials for relapsed elderly acute leukemia patients: Importance of performance status at re-induction. A single center retrospective experience

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 6575-6575
Author(s):  
W. J. Van Heeckeren ◽  
P. Fu ◽  
P. Barr ◽  
M. Laughlin ◽  
W. Tse ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Acute Leukemia ◽  
Phase I ◽  
Induction Chemotherapy ◽  
Performance Status ◽  
Univariate Analysis ◽  
Outcome Data ◽  
University Hospitals ◽  
Ecog Performance Status ◽  
Serious Adverse Events

6575 Background: Relapsed/refractory acute leukemia patients (pts) have a poor outcome and should be considered for enrollment on clinical trials. Elderly (≥ 60 yr) acute leukemia patients often are excluded from phase I/II cytotoxic agent re-induction chemotherapy trials due to concerns for treatment-related toxicity. Methods: Pts with relapsed/refractory acute leukemia who were enrolled on three consecutive phase I/II clinical trials at University Hospitals of Cleveland were evaluated for outcome data including complete response (CR), serious adverse events, and overall survival (OS). Outcome data was compared for pts age ≥ 60 yr versus < 60 yr. Pts with ECOG Performance Status (PS) 0 to 3 were eligible and there was no age limitation. Results: Between 1994 and 11/2005, 96 acute leukemia pts median age 60 yr (range 19–78) were enrolled: 29 pts received phase I topotecan-etoposide; 31 pts received phase I fludarabine, carboplatin, and topotecan (FCT); and 37 pts received phase II FCT plus thalidomide. In univariate analysis, PS at therapy initiation, mean # prior treatments, and disease status at time of treatment were not statistically different between older and younger pts ( Table ). Using Kaplan-Meier method, early treatment-related mortality and OS were similar in pts age ≥ 60 yr compared to pts < 60 yr ( Table ). Mean # ≥ grade 3 toxicities and CR also were similar in both groups ( Table ). In univariate (p = 0.001) and multivariate (p = 0.0004) analyses by Cox modeling, pts PS 0–1 had better OS than PS 2–3 (PS 0–1: 30-day survival 98% and 1 yr survival 24% versus PS 2–3: 30-day survival 81% and 1 yr survival 6%). Conclusions: Poor PS is an important negative predictor of outcomes in relapsed/refractory acute leukemia pts. Advanced age should not exclude pts from cytotoxic re-induction chemotherapy trials. [Table: see text] No significant financial relationships to disclose.

A phase I trial of concurrent chemoradiotherapy (cCRT) with the conventional administration of docetaxel (D) and cisplatin (P) for dry-stage III non-small cell lung cancer (NSCLC) (JCOG9901DI)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 7549-7549
Author(s):  
N. Hida ◽  
S. Tsujimura ◽  
T. Fujii ◽  
K. Naoki ◽  
H. Kunikane ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Trial ◽  
Performance Status ◽  
Objective Response ◽  
Locally Advanced ◽  
Recommended Dose ◽  
Stage Iii ◽  
Ecog Performance Status ◽  
Full Dose ◽  
Level 2

7549 Background: In cCRT for locally advanced NSCLC, full dose chemotherapy with a new agent plus a platinum doublet is considered to have unacceptable toxicities. Consequently, weekly or split chemotherapy doses are often used. However, cCRT plus conventional regimens are expected to enhance systemic effects. This phase I trial aimed to establish the MTD of cCRT plus conventional administration of DP (conv-DP). Methods: Unresectable stage III NSCLC patients (pts) (<70 years) with ECOG performance status 0–1 and adequate organ function were eligible. Pts received 60 Gy in 30 fractions by once daily radiotherapy. Concurrent P (day1; 60 mg/m2 at levels 1–3, 80 mg/m2 at level 4) and D (day1; 30 mg/m2 at level 1, 40 mg/m2 at level 2, 50 mg/m2 at levels 3–4) were given every 4 weeks for at least 2, and up to 4 courses. DLT was defined as either Gr3/4 febrile neutropenia, Gr4 neutropenia lasting ≥ 4 days, Gr4 thrombocytopenia, Gr2 pneumonitis or any Gr3 non-hematological toxicities except for nausea, vomiting and alopecia. Results: Eighteen pts were enrolled from 06/1999 to 05/2006: 6 pts at levels 2 and 4, 3 pts at levels 1 and 4; 13 males; median age 60 years (range 43–70); stage IIIA/IIIB 5/13; histology Ad/Sq/Large 9/7/2. DLTs were observed for 3 pts at level 2 (D40/P60): Gr4 pneumonitis at level 3(D50/P60), Gr3 cerebral infarction and Gr3 atrial fibrillation. Although 3 cases were added at these levels, tolerability for each level was cleared, as DLTs occurred for ≤ 2 pts among 6. MTD was not detected, even at the highest dose (D50/P80). However, dose escalation was stopped, as D60/P80 was the recommended dose for chemotherapy alone in Japan. Radiotherapy (60 Gy) was completed for 15 pts. Seventeen pts received more than 2 courses of chemotherapy. No Gr3/4 esophagitis or severe hematologic toxicities were observed. Objective response rate was 89% and 1-yr survival rate was 55%. Conclusions: The recommended dose in this regimen was D50/P80, which was near the full dose for conv-DP. Based on these promising results, we are planning a phase II trial to evaluate the efficacy and toxicity of this cCRT with conv-DP therapy. No significant financial relationships to disclose.

First results of induction chemotherapy with cisplatin, docetaxel, and capecitabine for the treatment of nasopharyngeal carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 6045-6045
Author(s):  
Y. Beldjilali ◽  
K. A. Benhadji ◽  
A. Boukerche ◽  
H. Khellafi ◽  
A. Abdelaoui ◽  
...  
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Induction Chemotherapy ◽  
Tumor Response ◽  
Performance Status ◽  
Locally Advanced ◽  
High Response Rate ◽  
Induction Treatment ◽  
Ecog Performance Status ◽  
P 75 ◽  
Grade 3

6045 Background: The purpose of this phase II study is to assess a new induction chemotherapy regimen combining cisplatin (P), docetaxel (T), and capecitabine (X) in advanced nasopharyngeal carcinoma. Methods: Previously untreated patients (pts) with histological diagnosed locally advanced nasopharyngeal carcinoma (stages III, IVA, and IVB UICC 2002) received induction chemotherapy associating P 75 mg/m2, T 75 mg/m2, both on day 1 and X 1,000 mg/m2/d days 1–14. Cycles were repeated every 3 weeks. A total of 4 cycles was planned for each patient. Induction chemotherapy was followed by concurrent chemo-radiotherapy: P 75 mg/m2 days 1, 22, 42 and radiotherapy (65–70 Gy) 4 to 6 weeks after the fourth cycle of induction treatment. Primary end point was tumor response of the induction regimen. Pts were evaluated according to RECIST criteria by clinical examination and CT scan of the nasopharynx. Results: 40 pts (26 male and 14 female) were enrolled. Median age was 40 years (range 18–56), ECOG performance status was 0–1 in all pts. 30 pts (75%) had an undifferentiated carcinoma of nasopharyngeal type (UCNT) and 10 pts (25%) a poorly differentiated nasopharyngeal carcinoma. 5 pts had stage III disease, 20 pts stage IVA disease and 15 pts stage IVB. Toxicity and tumor response were assessable in 40 pts. After 160 cycles, grade 3–4 toxicities (NCI-CTC 3.0) were: neutropenia (11 %), anemia (10.5%), nausea and vomiting (28%), diarrhea (8%), mucositis (3%), reversible alopecia (100%), and fatigue (10%). No febrile neutropenia was noted. 2 pts had grade 3 renal toxicity and only one patient had hand-foot syndrome (grade 3). Response rates for the 40 pts were: complete response 48%, partial response 40%, stable disease 4%, and progressive disease 8%. Conclusions: PTX induction chemotherapy resulted on a high response rate with manageable toxicity. Outcome of patients after chemoradiotherapy is awaited to evaluate the effectiveness of this new treatment modality. No significant financial relationships to disclose.

Phase I results of the randomized, placebo controlled, phase I/II study of the novel oral c-Met inhibitor, ARQ 197, irinotecan (CPT-11), and cetuximab (C) in patients (pts) with wild-type (WT) KRAS metastatic colorectal cancer (mCRC) who have received front-line systemic therapy.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 527-527 ◽  
Author(s):  
C. Eng ◽  
J. C. Bendell ◽  
A. Bessudo ◽  
N. Y. Gabrail ◽  
J. Diamond ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Performance Status ◽  
Locally Advanced ◽  
Standard Of Care ◽  
Complete Response ◽  
Ecog Performance Status ◽  
Tumor Cell Migration ◽  
Arq 197 ◽  
Grade 3

527 Background: ARQ 197 selectively inhibits the c-Met receptor tyrosine kinase (RTK), which has been implicated in tumor cell migration, invasion, proliferation, and angiogenesis. CPT-11 plus C is a standard of care for CPT-11-refractory mCRC pts with WT KRAS tumors. Resistance to C has been associated with activation of alternative RTK pathways including c-Met. We hypothesize that adding ARQ 197 to CPT-11 plus C may decrease resistance to C therapy and improve pt outcomes. Methods: The primary objectives of phase I were to evaluate safety and tolerability of ARQ 197 administered in combination with CPT-11 plus C, and to define a recommended phase II dose (RPTD). Pts with surgically unresectable locally advanced or mCRC who received at least 1 prior line of chemotherapy, KRAS WT and ECOG performance status < 2 were eligible. Cohorts of 3 pts each were treated with CPT-11 (180 mg/m2) and C (500 mg/m2) every 2 weeks along with escalating doses of ARQ 197 (120, 240, 360 mg) PO BID. Blood and tissue were collected for PK, biomarker, and other analyses. If no DLTs were observed during the first 28-day cycle in 3 pts treated in cohort 3, 360 mg BID would be defined as the RPTD. Responses were assessed every 8 weeks per RECIST v1.1. Results: Nine pts were treated in 3 cohorts. Median age: 53 yrs (range 30-77); ECOG PS 0/1: 4/5; median prior therapies: 2 (range 1-4). No DLTs were observed. The RPTD for ARQ 197 was 360 mg BID. To date, two pts have discontinued (1 disease progression and 1 withdrew consent after achieving complete response) and 7 pts remain on study. The reported grade 3/4 adverse events were: neutropenia (3/4: 1/1), and one case each of grade 3 fatigue, leucopenia, acneiform rash, vomiting, anemia and syncope. Preliminary efficacy data in 9 evaluable pts include 1 CR (after 4 cycles), 2 PR (after 2 cycles), 5 SD, and 1 PD as best response. Conclusions: The combination of ARQ 197 and CPT-11 plus C was well tolerated with encouraging preliminary antitumor activity. The RPTD for ARQ 197 was 360 mg BID. The randomized phase II portion of the study continues accrual. [Table: see text]

NRG Oncology NRG-GI007 trial-in-progress: Phase I study of OBP-301 (Telomelysin) and definitive chemoradiation (CRT) for patients with locally advanced esophageal and gastroesophageal adenocarcinoma who are not candidates for surgery.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. TPS262-TPS262
Author(s):  
Geoffrey Yuyat Ku ◽  
Kathryn A. Winter ◽  
Terence Marques Williams ◽  
Prasad S. Adusumilli ◽  
Makoto Nishimura ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Performance Status ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Human Adenovirus ◽  
Adenovirus Type ◽  
Ecog Performance Status ◽  
Human Telomerase Reverse Transcriptase ◽  
Definitive Therapy

TPS262 Background: Definitive CRT is a standard-of-care for patients with medically inoperable esophageal cancer (EC, NEJM 326:1593). The NRG/RTOG 0436 study of cisplatin/paclitaxel and RT (+/- cetuximab) as definitive therapy showed that about ½ of patients have locally persistent disease (JAMA Oncol 3:1520). OBP-301 is a conditionally-restricted, replication-competent adenovirus derived from human adenovirus type 5 (Ad-5) that adds a human Telomerase Reverse Transcriptase (hTERT) gene promoter; it replicates only in tumor cells to cause lysis. It may enhance RT and may cause immunogenic cell death. A phase I study with RT in Japanese patients with inoperable EC showed tolerability and activity. Methods: In NRG-GI007, OBP-301 is added to weekly carboplatin/paclitaxel and RT to 50.4 Gy (1.8 Gy/fx ×28 fx) for patients with medically inoperable esophageal or gastroesophageal junction (GEJ) adenocarcinoma. Patients receive intratumoral OBP-301 1×1012 virus particles (vp)/ml via endoscopy (EGD) 3 days prior to CRT, then at days 12 and 26 of CRT, for a total of 3 doses. Restaging with PET and EGD occur 6-8 weeks later. Blood and tumor tissue are collected for immune- and viral-based correlative assays. Patients must be assessed to be medically inoperable and have ECOG performance status <1. The primary endpoint is safety, and clinical complete response (cCR) rate is a secondary endpoint. Initially, 6 patients are enrolled. If protocol-defined dose-limiting toxicity (DLT) occurs in <1 of 6 patients, the dose will be deemed to be safe and 9 more will be enrolled to further assess safety and obtain a preliminary assessment of cCR rate. If >2 of 6 patients have DLT, the dose of OBP-301 is reduced to 1×1011 vp/ml and another 6 patients will be treated. If <1 of 6 patients has a DLT at the lower dose, that dose will be deemed to be safe and 9 more will be enrolled. If >2 of 6 patients have DLT, then neither dose level will have met the safety rule and the trial will be ended. This trial opened to accrual on June 29, 2020. Clinicaltrials.gov NCT04391049. Funding: This project was supported by grants U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), U24CA180803 (IROC), from the National Cancer Institute (NCI) and Oncolys BioPharma. Clinical trial information: NCT04391049.

Induction chemotherapy with docetaxel, cisplatin, fluorouracil, and leucovorin for squamous cell carcinoma of the head and neck: a phase I/II trial.

1998 ◽  
Vol 16 (4) ◽  
pp. 1331-1339 ◽  
Author(s):  
A D Colevas ◽  
P M Busse ◽  
C M Norris ◽  
M Fried ◽  
R B Tishler ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Peripheral Neuropathy ◽  
Phase I ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Induction Chemotherapy ◽  
Squamous Cell ◽  
Performance Status ◽  
Locally Advanced ◽  
Eastern Cooperative Oncology Group

PURPOSE A phase I/II trial of docetaxel, cisplatin, fluorouracil (5-FU), and leucovorin (TPFL5) induction chemotherapy for patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS Twenty-three previously untreated patients with stage III or IV SCCHN and Eastern Cooperative Oncology Group functional status less than or equal to 2 were treated with TPFL5. Postchemotherapy home support included intravenous fluids, prophylactic antibiotics, and granulocyte colony-stimulating factor (G-CSF). Docetaxel dose was escalated to determine the maximum-tolerated dose (MTD). Fifteen patients were treated with three cycles of TPFL5 at MTD. Patients who achieved either a partial response (PR) or complete response (CR) to three cycles of TPFL5 then received definitive twice-daily radiation therapy. Toxicity and clinical and pathologic response to TPFL5 were assessed. RESULTS Twenty-three patients received a total of 69 cycles of TPFL5. The MTD was determined to be docetaxel 60 mg/m2. Dose-limiting toxicity (DLT) was neutropenia. Additional significant toxicities at MTD were nausea, mucositis, diarrhea, peripheral neuropathy, and sodium-wasting nephropathy. The overall response rate to TPFL5 was 100%, which included 14 of 23 (61%) clinical CRs and nine of 23 (39%) clinical PRs. Primary-site clinical and pathologic CR rates were 19 of 22 (86%) CRs and 20 of 22 (91%) CRs, respectively. Eight patients had less than a CR in the neck to chemotherapy and, therefore, had postradiation neck dissections, four of which were positive for residual tumor. CONCLUSION TPFL5 is a tolerable induction regimen in patients with good performance status. The DLT is neutropenia with significant mucositis, diarrhea, peripheral neuropathy, and sodium-wasting nephropathy. The high response rates to TPFL5 justify further evaluation of this combination of agents in the context of formal clinical trials.

Avelumab (MSB0010718C), an anti-PD-L1 antibody, as a third-line treatment in patients with advanced gastric or gastroesophageal junction cancer: A phase Ib JAVELIN Solid Tumor trial.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. TPS188-TPS188 ◽  
Author(s):  
Do-Youn Oh ◽  
Albert C. Lockhart ◽  
Deborah Jean Lee Wong ◽  
Matthew Hiram Taylor ◽  
Marcis Bajars ◽  
...  
Keyword(s):  
Performance Status ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Progression Free Survival ◽  
Her2 Status ◽  
Open Label ◽  
Ecog Performance Status ◽  
Phase Ib ◽  
Prior Therapy ◽  
Recist 1.1

TPS188 Background: The programmed death-1 receptor (PD-1) and its ligand (PD-L1) are key therapeutic targets in the reactivation of the immune response against cancer. Avelumab* (MSB0010718C) is a fully human anti-PD-L1 IgG1 antibody being investigated in clinical trials. The phase Ib study (NCT01772004) is an open-label, parallel-group expansion trial in patients (pts) with locally advanced or metastatic (LA/M) solid tumors that includes a heavily pretreated cohort of pts with advanced gastric or gastroesophageal junction adenocarcinoma (GC/GEJ) to evaluate safety and efficacy of avelumab in the 3rd-line setting. Prior to adding this 3rd-line cohort, this trial had enrolled a separate cohort with advanced GC/GEJ who had received prior 1st-line chemotherapy (Chung et al, ECC 2015). Methods: This trial cohort is enrolling pts with histologically confirmed unresectable LA/M GC/GEJ who have been previously treated with 1st-line combination chemotherapy and 2nd-line ramucirumab, alone or in combination, and whose disease has progressed during or after ramucirumab treatment. Pts who have received prior treatment with trastuzumab and pts with HER2+ status are allowed. Eligible pts also must have tumor archival material or fresh biopsy, an ECOG performance status of 0 or 1 at the time of trial entry, and disease with ≥ 1 measurable lesion according to RECIST 1.1. Exclusions include prior therapy with immune checkpoint drugs or history of autoimmune disease. Up to 150 eligible pts will receive avelumab at 10 mg/kg as an IV infusion Q2W. Treatment will continue until disease progression, unacceptable toxicity, or any criterion for withdrawal occurs. Primary endpoint is confirmed best overall response (RECIST 1.1) as adjudicated by an IERC. Secondary objectives include assessment of progression-free survival, overall survival, and immune-related efficacy assessments. Association between tumor PD-L1 expression and efficacy will be evaluated. Adverse events will be assessed and graded according to NCI-CTCAE v4.0. Tumor evaluation will be performed every 6 wks until progression. Enrollment in this cohort began in June 2015. *Proposed INN Clinical trial information: NCT01772004.

A Phase I Study of OMN54 (Aneustat™) in Patients with Advanced Malignancies

2020 ◽  
Vol 7 (2) ◽  
pp. 125-132
Author(s):  
Karen A. Gelmon ◽  
Christian Kollmannsberger ◽  
Stephen Chia ◽  
Anna V. Tinker ◽  
Teresa Mitchell ◽  
...  
Keyword(s):  
Phase I ◽  
Salvia Miltiorrhiza ◽  
Performance Status ◽  
Parent Drug ◽  
Maximum Tolerated Dose ◽  
Ecog Performance Status ◽  
Advanced Malignancies ◽  
Gi Toxicity ◽  
Adequate Organ Function ◽  
Recommended Phase Ii Dose

Background/Objective: With the increasing interest in natural products, a phase I openlabel study of OMN54 (Aneustat™) in patients with advanced malignancies was initiated to determine toxicity, maximum tolerated dose (MTD), dose limiting toxicities (DLT), and pharmacokinetics (PK). OMN54 is a multitargeted agent, combining three Chinese botanicals; Ganoderma lucidium, Salvia miltiorrhiza and Scutellaria barbata. Methods: Eligible patients (pts) were >18 years of age with advanced solid tumors, able to swallow oral capsules, ECOG performance status < 2, measurable disease as defined by RECIST 1.1 and adequate organ function. Results: Twenty-two patients were enrolled in 6 dose levels, 2 with daily dosing and 4 with twicedaily dosing ranging from 1 to 5 grams daily. All were evaluated for toxicity and 20 for response. No treatment-related dose-limiting toxicities (DLTs) were reported and the recommended phase II dose (RP2D) was determined to be 2.5 g twice daily. Seven adverse events in 5 patients were reported as possibly drug-related; 6 were GI toxicity and 1 was a skin disorder. All were grade 1 except one grade 2 vomiting. No RECIST responses were seen. Six pts were treated with > 2 cycles; one for 8 cycles. Four patients had reductions in TGF –β and EGF, exploratory biomarkers possibly suggestive of a drug effect. Plasma half-lives of 1 -2 hours were noted for all parent drug chemical markers with no accumulation over time. Conclusion: OMN54 was well tolerated, with no DLTs observed. Further studies at the RP2D will assess the biological activity.

Phase I Trial of Escalating-Dose Irinotecan Given Weekly With Cisplatin and Concurrent Radiotherapy in Locally Advanced Esophageal Cancer

2003 ◽  
Vol 21 (15) ◽  
pp. 2926-2932 ◽  
Author(s):  
David H. Ilson ◽  
Manjit Bains ◽  
David P. Kelsen ◽  
Eileen O’Reilly ◽  
Martin Karpeh ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Phase I ◽  
Induction Chemotherapy ◽  
Phase Ii ◽  
Phase I Trial ◽  
Locally Advanced ◽  
Phase Iii ◽  
Concurrent Radiotherapy ◽  
Minimal Toxicity ◽  
Grade 3

Purpose: To identify the maximum-tolerated dose and dose-limiting toxicity (DLT) of weekly irinotecan combined with cisplatin and radiation in esophageal cancer. Patients and Methods: Nineteen patients with clinical stage II to III esophageal squamous cell or adenocarcinoma were treated on this phase I trial. Induction chemotherapy with weekly cisplatin 30 mg/m2 and irinotecan 65 mg/m2 was administered for four treatments during weeks 1 to 5. Radiotherapy was delivered weeks 8 to 13 in 1.8-Gy daily fractions to a dose of 50.4 Gy. Cisplatin 30 mg/m2 and escalating-dose irinotecan (40, 50, 65, and 80 mg/m2) were administered on days 1, 8, 22, and 29 of radiotherapy. DLT was defined as a 2-week delay in radiotherapy for grade 3 to 4 toxicity. Results: Minimal toxicity was observed during chemoradiotherapy, with no grade 3 or 4 esophagitis, diarrhea, or stomatitis. DLT caused by myelosuppression was seen in two of six patients treated at the 80-mg/m2 dose level, thus irinotecan 65 mg/m2 was defined as the recommended phase II dose. Dysphagia improved or resolved after induction chemotherapy in 13 (81%) of 16 patients who reported dysphagia before therapy. Only one patient (5%) required a feeding tube. Six complete responses (32%) were observed, including four pathologic complete responses in 15 patients selected to undergo surgery (27%). Conclusion: Cisplatin, irinotecan, and concurrent radiotherapy can be administered on a convenient schedule with relatively minimal toxicity and an acceptable rate of complete response in esophageal cancer. Further phase II evaluation of this regimen is ongoing. A phase III comparison to fluorouracil or taxane-containing chemoradiotherapy should be considered.

Phase I study of repeated cycles of high-dose cyclophosphamide, etoposide, and cisplatin administered without bone marrow transplantation.

1990 ◽  
Vol 8 (10) ◽  
pp. 1728-1738 ◽  
Author(s):  
J A Neidhart ◽  
W Kohler ◽  
C Stidley ◽  
A Mangalik ◽  
A Plauche ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Phase I ◽  
Performance Status ◽  
Complete Response ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Tumor Type ◽  
Advanced Malignancy ◽  
Prior Therapy ◽  
And Performance

Forty-two patients with advanced malignancy judged unlikely to respond to standard treatment received high-dose combination chemotherapy with cyclophosphamide, etoposide, and cisplatin in a phase I trial. Twenty-two of these patients who had at least a partial response (PR) to the first cycle of therapy received a second cycle, and eight patients received three or more cycles of therapy. Bone marrow replacement was not used. The maximum-tolerated doses (MTDs) were cyclophosphamide 2.5 g/m2 on days 1 and 2; etoposide 500 mg/m2 on days 1, 2, and 3; and cisplatin 50 mg/m2 on days 1, 2, and 3. Hematologic toxicity was not dose-limiting by study design. Recovery to an absolute granulocyte count above 100/microL occurred at a median of 9 days from onset (range, 3 to 23 days) at the MTD. Recovery was delayed after the third cycle. Only one patient on his third cycle failed to recover peripheral blood counts and died of sepsis an day 43. Hematologic toxicity was not dose-dependent. Nonhematologic toxicities included emesis, fatigue, alopecia, diarrhea, and anorexia and were generally well tolerated. The dose-limiting toxicities were fatal pulmonary or cardiac toxicities in five of nine patients treated at the highest dose level. Patients likely to do well can be selected by tumor type, response to prior therapy, and performance status. Nine of 36 assessable patients had a complete response (CR) and 13 a PR for a response rate of 61%. Five patients (12%) remain alive and free of disease at 15 to 32 months. Repeated cycles of dose-intensive combination therapy can produce long-term disease-free remissions in patients with refractory tumor types. The toxicity of the regimen is acceptable if patients are carefully selected.

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