Phase I study of weekly albumin-bound paclitaxel (ab-P) plus weekly cetuximab (Cet) plus intensity-modulated radiation therapy (IMRT) in patients with stage III/IVb head and neck squamous cell carcinoma (HNSCC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 6034-6034 ◽  
Author(s):  
Matthew G. Fury ◽  
Eric Jeffrey Sherman ◽  
Shyam S. Rao ◽  
Suzanne L. Wolden ◽  
Stephanie Smith-Marrone ◽  
...  
Keyword(s):  
Oral Cavity ◽  
Phase I ◽  
Phase I Study ◽  
Intensity Modulated Radiation Therapy ◽  
Maximum Tolerated Dose ◽  
Stage Iii ◽  
Unknown Primary ◽  
Neck Node ◽  
Entire Study ◽  
Recommended Phase Ii Dose

6034 Background: There is a clinical need to improve the efficacy of standard Cet + concurrent RT for pts with stage III/IVB HNSCC. Taxanes have potent activity against HNSCC, and ab-P may offer therapeutic advantages in comparison with other drugs of this class. Methods: This was a single institution phase I study with a modified 3 + 3 design. 4 dose levels (DLs) of weekly ab-P were explored (30, 45, 60, and 80 mg/m2) during IMRT. Standard Cet (450 mg/m2 loading dose followed by 250 mg/m2 weekly) concurrent with IMRT (total dose, 70 Gy) was prescribed for all pts. The maximum-tolerated dose (MTD) would be exceeded if >2/6 pts experienced DLTs at a given dose level. NCI CTCAE v.3 was used, and DLT monitoring extended until 2 wks after IMRT. Results: 25 eligible pts (20M, 5F) enrolled, with median age 58 years (range, 46-84) and median KPS 90 (range 80-100). Primary tumor sites were oropharynx, 20 (10 HPV pos, 5 HPV neg, 5 not done); neck node with unknown primary, 2; and larynx, oral cavity, and maxillary sinus, 1 each. Two pts never received ab-P and were deemed inevaluable. At DL 1 (ab-P, 30 mg/m2), there was one DLT (g.4 pneumonia) among 6 pts. At DL2 (ab-P, 45 mg/m2), there were 2 DLTs (g.4 cerebrovascular accident; g.3 decrease in L. ventricle ejection fraction/CHF exacerbation) among 6 pts. At DL3 (ab-P, 60 mg/m2), there was 1 DLT (g.3 supraventricular tachycardia) among 6 pts. MTD was exceeded at DL4 (ab-P, 80 mg/m2) with 3 DLTS (g.3 neuropathy, g.3 dehydration, g.3 anemia) among 5 evaluable pts. For the entire study population, most common ≥ g3 AEs were: lymphopenia 100%, functional mucositis, 56%, and pain in throat/oral cavity, 52%. There were no treatment-related deaths. Among 23 evaluable pts at a median follow up of 29 months, 2y PFS rate is 64% (95% CI: 41-80%) and 2y OS rate is 90% (95% CI: 66-97). Conclusions: The recommended phase II dose is ab-P 60 mg/m2 weekly when given concurrently with IMRT and standard weekly Cet. This regimen merits further study as an alternative to IMRT + Cet alone for pts who require a non-platinum regimen. This study was approved and funded by the NCCN from general research support provided by Celgene, Inc. Clinical trial information: NCT00736619.

Phase I study of c-Met inhibitor ARQ197 in combination with FOLFOX for the treatment of patients with advanced solid tumors.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2544-2544
Author(s):  
Suzanne Fields Jones ◽  
Carla Kurkjian ◽  
Manish R. Patel ◽  
Jeffrey R. Infante ◽  
Howard A. Burris ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Phase Ii ◽  
Stable Disease ◽  
Phase I Study ◽  
Standard Dose ◽  
Maximum Tolerated Dose ◽  
Unknown Primary ◽  
Advanced Solid Tumors ◽  
Grade 3

2544 Background: C-Met protein is a receptor tyrosine kinase which is overexpressed or mutated in a variety of tumor types, causing cell proliferation, metastasis, and angiogenesis. Tivantinib is an orally bioavailable small molecule which binds to the c-Met protein. This phase I study was designed to determine the maximum tolerated dose (MTD) of tivantinib in combination with standard dose FOLFOX for the treatment of patients with advanced solid tumors. Methods: Patients with advanced solid tumors for which FOLFOX (5-FU IV 400 mg/m2 day 1; 5-FU CIV 2400 mg/m2 day 1; Leucovorin IV 400 mg/m2 day 1; Oxaliplatin IV 85 mg/m2 day 1) would be appropriate chemotherapy received escalating doses of tivantinib BID (days 1-14) in a standard 3 + 3 design. Dose-limiting toxicities (DLTs), non-dose-limiting toxicities (NDLTs), safety, and preliminary efficacy were evaluated. Results: Fourteen patients (50% colorectal) were treated across 3 dose levels: 120 mg (n=3); 240 mg (n=5); 360 mg (n=6). No DLTs were observed until the 3rd dose level (treatment delay ≥3 days, secondary to grade 3 neutropenia). Common related adverse events (% grade 1/2; % grade 3/4) included: diarrhea (36%; 0%), neutropenia (0%; 29%), nausea (14%; 14%), vomiting (14%; 14%), dehydration (14%; 7%), and thrombocytopenia (14%; 0%). To date, 7 patients have been evaluated for response including 4 (57%) with stable disease evident at the 8-week evaluation (CRC, 2 patients; unknown primary favoring CRC, 1 patient; esophageal, 1 patient) and 3 (21%) with disease progression. The 4 patients with stable disease are continuing on treatment; three (CRC and unknown primary) had received prior FOLFOX. Conclusions: The addition of tivantinib to standard therapy FOLFOX appears tolerated up to its recommended phase II monotherapy dose of 360 mg. Preliminary efficacy is encouraging, and a phase II study is proceeding with this regimen for the first line treatment of advanced gastroesophageal patients. Clinical trial information: NCT01611857.

Phase I study of capecitabine combined with weekly carboplatin and intensity modulated radiation therapy (IMRT) for treatment of locally advanced squamous cell carcinomas of the head and neck (HNSCC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15522-15522
Author(s):  
C. Y. Thomas ◽  
P. Read ◽  
K. Sheng ◽  
D. Bliesner ◽  
P. Levine ◽  
...  
Keyword(s):  
Phase I ◽  
Locally Advanced ◽  
Intensity Modulated Radiation Therapy ◽  
Complete Response ◽  
Maximum Tolerated Dose ◽  
Stage Iii ◽  
Fixed Dose ◽  
Parotid Sparing ◽  
Grade 3 ◽  
Carboplatin Auc

15522 Background: Chemoradiotherapy (CRT) programs for locally advanced HNSCC that reduce toxicity but maintain efficacy are needed. Methods: A two-step phase I trial to determine the maximum tolerated dose (MTD) of capecitabine combined with fixed dose carboplatin, given prior to and during concomitant IMRT. Start dose of capecitabine =1500 mg/m2/d p.o. BID days 1–14 and 22–35 with carboplatin AUC =2 IV weekly x 6. With IMRT, the doses were adjusted to 1000 mg/m2/d and AUC =1.5, respectively. Parotid-sparing IMRT = 50 and 45 Gy/25 fractions to gross disease (GD) and low risk nodes, respectively; 3D conformal boost of 20 Gy/10 fractions to GD. Dose limiting toxicity (DLT) defined as ANC <750, ≥ grade 3/4 thrombocytopenia or selected non-hematologic toxicities. Results: 11 patients (pts) with stage III/IV (T2–4,N1–2C) HNSCCs of the oropharynx (7), oral cavity (2), both (1), or hypopharynx (1) were studied. 10/9 pts evaluable for toxicity after induction/concomitant chemotherapy, respectively; 2 pts had early disease progression (d22 and 43). During radiation, the MTD for capecitabine established as 825 mg/m2/d. At start dose, 2/3 pts developed thrombocytopenia as DLT; CRT-related toxicities = grade 3 mucositis (3), dysphagia (3), fatigue (1), anemia (1), and dermatitis (1). For induction chemotherapy, DLTs seen in 0/3 pts at capecitabine =1750 mg/m2 and 1/6 at lower doses (grade 4 diarrhea; no other Gr3/4 drug-related toxicities). Response of primary (or neck) tumors to induction: CR 3 (3), PR 6 (3), SD 1 (3), and PD 2 (2). After CRT, 8/9 pts achieved CR and are alive without disease (mean follow-up 6 months). Conclusions: Capecitabine 825 mg/ m2/d and carboplatin AUC =1.5 weekly given on the described schedule and in combination with IMRT produce moderate toxicity and a high complete response rate in stage III/IV HNSCC pts that received the same drugs as induction therapy. The latter combination was also well tolerated and had anti-tumor activity (capecitabine Y=1500–1750 mg/m2/d). Additional studies are warranted to determine if these regimens provide an effective but less toxic alternative to cisplatin or taxane-based CRT programs. Supported in part by Bristol-Myers-Squibb. No significant financial relationships to disclose.

Biweekly oxaliplatin with gemcitabine and capecitabine in advanced gastrointestinal malignancies: A phase I study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4560-4560
Author(s):  
B. R. Tan ◽  
W. S. Brenner ◽  
J. Picus ◽  
R. Suresh ◽  
S. Sorcher ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Maximum Tolerated Dose ◽  
Toxicity Assessment ◽  
Unknown Primary ◽  
Pharmacokinetic Studies ◽  
Gastrointestinal Malignancies ◽  
Constant Rate ◽  
Grade 3 ◽  
Triplet Regimen

4560 Background: Oxaliplatin (OX), gemcitabine (GEM) and capecitabine (CAP) are all active agents against various gastrointestinal and other malignancies and have different mechanisms of action and toxicity profiles. This Phase I study aims to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) associated with this triplet regimen. Methods: The modified Fibonacchi 3/cohort dose escalation schema was used to determine the MTD and DLT of OX, GEM and CAP. Oxalipaltin [85–100 mg/m2] IV over 2 hours and gemcitabine [800–1,000 mg/m2] were given at a constant rate infusion of 10 mg/m2/min on days 1 & 15, while CAP [600–800 mg/m2] was given PO BID on days 1–7 and 15–21. 1 cycle = 28 days. Pharmacogenomic correlates including ERCC2, GSTP1, TYMS, TS del and TSER G>C were also obtained. A structured neurological toxicity assessment and questionnaire was also performed. Once MTD was established, additional patients were treated at the MTD and pharmacokinetic studies were performed on these additional patients. Results: 30 patients (M:F 2:1; 23% non-caucasian) with median age of 62 (range: 38–78) and PS of 0–1 were enrolled from 3/05 to 8/06. All patients had advanced GI malignancies (19 pancreatic, 6 biliary, 2 duodenal, 1 gastric, 1 esophageal, 1 GI unknown primary). Dose levels, # patients, DLT and best responses are tabulated below. Conclusions: The MTD of this triplet regimen is OX at 100 mg/m2, GEM at 800 mg/m2 days 1 & 15 with CAP at 800 mg/m2 PO BID days 1–7, 15–21. DLTs for this regimen include grade 3 fatigue and dyspnea as well as Grade 4 thrombocytopenia. CR is achieved in 2 patients (cholangiocarcinoma and pancreatic), while a patient with a GI unknown primary achieved PR. Several patients with pancreatic cancer achieved prolonged SD. An exploration of any association of toxicities and response with pharmacogenomic correlates is ongoing. A Phase II study in patients with pancreaticobiliary cancers is planned. This study is supported by Sanofi-Aventis Pharmaceuticals. [Table: see text] [Table: see text]

scholarly journals Phase I study protocol: NKTR-255 as monotherapy or combined with daratumumab or rituximab in hematologic malignancies

2021 ◽  
Author(s):  
Nina Shah ◽  
Miguel-Angel Perales ◽  
Cameron J Turtle ◽  
Mitchell S Cairo ◽  
Andrew J Cowan ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Hematologic Malignancies ◽  
Maximum Tolerated Dose ◽  
Multiple Cancer ◽  
Cancer Models ◽  
Anti Cancer ◽  
Recommended Phase Ii Dose ◽  
And Function ◽  
Anti Tumor Activity

NKTR-255 is an investigational polyethylene glycol-modified recombinant human IL-15 (rhIL-15) receptor agonist, designed to improve the immunotherapeutic and anti-cancer benefit observed with rhIL-15 while circumventing the toxicities associated with this therapy. In preclinical studies, NKTR-255 has demonstrated enhanced proliferation and function of CD8+ T cells and natural killer cells, as well as enhanced anti-tumor activity and survival both as monotherapy and in combination with monoclonal antibodies in multiple cancer models. Here, we describe the rationale and design of the first-in-human Phase I, dose-escalation and dose-expansion study of NKTR-255 alone and in combination with daratumumab or rituximab in adults with relapsed/refractory multiple myeloma or non-Hodgkin's lymphoma that will determine the maximum tolerated dose and recommended Phase II dose for NKTR-255.

Phase I study of panitumumab, chemotherapy and intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC): Early results

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6083-6083 ◽  
Author(s):  
L. J. Wirth ◽  
M. R. Posner ◽  
R. B. TIshler ◽  
R. I. Haddad ◽  
L. Goguen ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Study ◽  
Intensity Modulated Radiotherapy ◽  
Sequential Therapy ◽  
Maximum Tolerated Dose ◽  
Radiation Dermatitis ◽  
Fixed Dose ◽  
Unknown Primary ◽  
Early Results ◽  
Egfr Antibody

6083 Background: Both chemotherapy and epidermal growth factor receptor (EGFR) antibody therapy improve outcomes in HNC when added to radiotherapy. This phase I study investigates the addition of the fully human anti-EGFR antibody, panitumumab, to chemoradiotherapy (CRT) for HNC. Methods: Treatment naïve adults with stage III/IV HNC (primary sites include oropharynx and unknown primary) with normal hematologic, renal, and liver function are currently enrolling in a 2-part study. Part A determines the maximum tolerated dose (MTD) of paclitaxel in 2 dose levels (DLs) (15 and 30 mg/m2 wkly×7 wks) with fixed-dose carboplatin and panitumumab (AUC of 1.5 and 2.5 mg/kg wkly, respectively) plus IMRT (70 Gy). Patients (pts) are enrolled in sets of 3. Part B determines the MTD of 5-FU in 2 DLs (800 and 900 mg/m2 days 1–4, Q21d) with fixed-dose docetaxel, cisplatin and panitumumab (75 mg/m2, 100 mg/m2 and 9 mg/kg, Q21d, respectively) for 3 cycles followed by panitumumab + CRT, as determined in Part A. Results: To date, 8 pts (n=3 at DL 1, n=5 at DL 2) have enrolled in Part A. One dose-limiting toxicity has occurred in DL 2: grade (gr) 4 febrile neutropenia. Other adverse events include gr 3/4 mucositis (n=6), gr 3/4 radiation dermatitis (n=6), gr 2 acneiform rash (n=6), gr 3 dysphagia (n=6) and gr 2 oral pain (n=6). Dose-reduction has not been necessary thus far. Enrollment will continue in a cohort of 10 pts in DL 2. Of 4 pts evaluated for response, 4 had complete response in the primary and neck, and 1 had a residual neck mass. This pt had 1 positive node on neck dissection. Conclusions: Preliminary results suggest that panitumumab can be added to CRT for treatment of HNC without magnifying the expected toxicities with CRT. Part B will investigate panitumumab + sequential therapy for HNC once the MTD of Part A is established. No significant financial relationships to disclose.

Open-label, multicenter, phase I study to assess safety and tolerability of adavosertib plus durvalumab in patients with advanced solid tumors.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2562-2562 ◽  
Author(s):  
Manish R. Patel ◽  
Gerald Steven Falchook ◽  
Judy Sing-Zan Wang ◽  
Esteban Rodrigo Imedio ◽  
Sanjeev Kumar ◽  
...  
Keyword(s):  
Phase I ◽  
Solid Tumors ◽  
Phase I Study ◽  
Human Monoclonal Antibody ◽  
Maximum Tolerated Dose ◽  
Preliminary Evidence ◽  
Advanced Solid Tumors ◽  
Open Label ◽  
Drug Induced ◽  
Recommended Phase Ii Dose

2562 Background: Adavosertib (AZD1775; A) is a highly selective inhibitor of WEE1. This Phase I study (NCT02617277) investigated a range of doses and schedules for oral A plus IV durvalumab (DV), a human monoclonal antibody targeting PD-L1, to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) in patients (pts) with advanced solid tumors. Methods: Four 28-day schedules (Sch) were evaluated with pts receiving DV 1500 mg on day (d) 1 of each schedule (Table). Patients continued treatment if they showed clinical benefit in the absence of any discontinuation criteria. Pts received A monotherapy for PK analysis prior to the start of combination therapy in Sch B, C (d –7 to –5) and D (d –9 to –5). MTD was determined using a 3+3 dose-escalation cohort design. Predefined dose-limiting toxicities (DLTs) were evaluated during the first cycle of study treatment. Results: 54 pts received A (most common primary tumor sites: colon, 19%; lung, 13%; breast, 11%). The most common grade ≥3 AEs were fatigue (15%), diarrhea (11%) and nausea (9%). DLTs were nausea (n = 2) and diarrhea (n = 1). 7 pts (13%) had A-related SAEs, including reversible and confounded drug-induced liver injury (Sch B 125 mg and Sch C; 1 each). Disease control rate (DCR) for the total cohort was 36%. Preliminary PK at 150 mg BID suggests adequate coverage for cell kill activity and no drug–drug interaction. Conclusions: The MTD/RP2D was A 150 mg BID (3 d on, 4 d off; treatment d 15–17, 22–24) with DV 1500 mg (d 1 Q4W); safety profile was considered acceptable. Preliminary evidence of antitumor activity was observed. Clinical trial information: NCT02617277. [Table: see text]

Phase I study to determine tolerability and pharmacokinetics (PK) of SB-743921, a novel kinesin spindle protein (KSP) inhibitor

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 2000-2000 ◽  
Author(s):  
K. D. Holen ◽  
C. P. Belani ◽  
G. Wilding ◽  
S. Ramalingam ◽  
J. L. Heideman ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Phase I Study ◽  
Tumor Regression ◽  
Human Tumor ◽  
Maximum Tolerated Dose ◽  
Potent Inhibition ◽  
Elevated Bilirubin ◽  
Recommended Phase Ii Dose ◽  
Tumor Types

2000 Background: SB-743921, a potent and selective inhibitor of KSP (Ki =100 pM; >40,000-fold selectivity vs other kinesins), causes mitotic arrest, potent inhibition of tumor cell proliferation, and demonstrates activity in a broad range of human tumor xenografts. Methods: A phase I study was conducted to determine the maximum tolerated dose (MTD) and PK profile of SB-743921 when administered IV over 60 minutes every 21 (Q 21) days (d). Results: 44 patients (pts) (M/F 19/25), median age 61.5 yrs (range 32–80, with solid tumors were treated at doses of 2 (n=2), 4 (n=27), 5 (n=6), 6 (n=3), and 8 (n=6) mg/m2 (median cycles 2, range 1–10, total cycles 101). Frequent tumor types included colorectal (n=11), ovarian (n=5), NSCLC (n=5), esophageal (n=4), and pancreatic (n=4). Dose-limiting toxicities (DLTs) at 8 mg/m2 consisted of (max CTC grade/pt) prolonged grade (gr) 4 neutropenia (n=2), gr 3 elevated ALT/AST (n=1), and gr 3 elevated bilirubin (n=1). DLTs at 6 mg/m2 were gr 3 hyponatremia (n=1) and prolonged gr 4 neutropenia (n=1). DLTs at 5 mg/m2 were limited to febrile neutropenia (n=2). The 4 mg/m2 dose level was determined as the phase II dose. Toxicities at 4 mg/m2 included gr 1 fatigue (n=8) and neutropenia [gr 1 (n=4), gr 2 (n=7), gr 3 (n=3), gr 4 (n=2)]. Neutropenia nadir was day 6–8 with recovery to gr ≤2 by day 15. Gr 3 non-hematologic toxicities at 4 mg/m2 included gr 3 ALT (n=1), gr 3 AST (n=2), gr 3 hyperbilirubinemia (n=1), gr 3 hypophosphatemia (n=1), and gr 3 alkaline phosphatase elevation (n=1). Median PK values in cycle 1 at 4 mg/m2 were: Cmax 473 ng/ml, AUC0-∞ 5207 ng.hr/ml, and t½ 36 hr. AUC0-∞ and Cmax were proportional to dose. No consistent correlation was observed between DLTs and PK parameters. Stable disease for ≥ 4 cycles (range 4–11) was observed in 6 pts (4 pts at 4 mg/m2; 1 pt at 6 mg/m2; 1 pt at 8 mg/m2). A pt with cholangiocarcinoma had evidence of radiographic tumor regression (post cycle 10) and a >50% decrease in her CA 19–9. Conclusions: The recommended phase II dose of SB-743921 on the Q 21 day schedule is 4 mg/m2. The observed toxicities at the recommended phase II dose are manageable and reversible. The onset and duration of neutropenia is predictable. [Table: see text]

A phase I study of everolimus (E) plus weekly cisplatin (CDDP) plus intensity-modulated radiation therapy (IMRT) in head and neck (HN) cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 5545-5545
Author(s):  
Matthew G. Fury ◽  
Eric Jeffrey Sherman ◽  
Alan Loh Ho ◽  
Shyam S. Rao ◽  
Ronglai Shen ◽  
...  
Keyword(s):  
Phase I ◽  
Dose Escalation ◽  
Phase I Study ◽  
Intensity Modulated Radiation Therapy ◽  
Failure To Thrive ◽  
Unknown Primary ◽  
Oral Pain ◽  
Increased Risk ◽  
Clinical Models ◽  
Grade 3

5545^ Background: The PI3K/mTOR/eIF4E pathway is upregulated in many HN cancers, and expression of eIF4E in surgical margins has been associated with increased risk of recurrence (Cancer Res 2007; 67:2160. Clin Cancer Res 2004; 10:5820. JCO 1999; 17:2909). Daily E + weekly CDDP was well tolerated in a phase I study for patients with advanced solid tumors (Cancer Chemother Pharmacol 2011 Sep 13; Epub ahead of print]. E achieves radiosensitization in pre-clinical models. This study evaluated weekly CDDP + daily E given concurrently with IMRT in HN cancer. Methods: This was a single institution phase I study with a standard 3 + 3 dose escalation plan. Patients (pts) received standard definitive IMRT (66 Gy resected tumors, 70 Gy unresected tumors) concurrent with CDDP 30 mg/m2 weekly X 6 and daily oral E according to the dose escalation plan. Four dose levels (DLs) of daily oral E were planned: 2.5 mg, 5 mg, 7.5 mg, and 10 mg. Toxicities were recorded according to NCI CTCAE v.3. Results: Thirteen (9M, 4F) pts enrolled, with median age 52y (range, 37 – 65y) and median KPS 90 (range, 80-100). Primary sites: oral cavity (4), salivary gland (4), oropharynx (2), nasopharynx (1), scalp (1), unknown primary (1). Stage: IVA (11), IVB (1), II (1). Prior treatment: surgery (10), chemotherapy (2). The most common ≥ G.3 treatment related AEs were mucositis (functional 62%, clinical 31%), oral pain (31%), and lymphopenia (31%). There were no DLTs among 3 patients at DL1 or the first 3 patients at DL2. Among 4 pts at DL3, there were 2 DLTs: grade 3 mucositis with failure to thrive, and grade 3 mucositis with hypoxia. Among 3 additional patients enrolled at DL2, there was one 1 DLT: grade 3 mucositis with inability to tolerate E. There were no treatment-related deaths. With a median follow-up of 8.9 months, 3 patients have experienced recurrent disease, one of whom has died of disease. Median PFS has not been reached. Tissue correlates in process. Conclusions: When administered with weekly CDDP (30 mg/m2) and definitive IMRT for HN cancer, the phase II recommended dose of E is 5 mg/day.

Phase I study of vinorelbine, cisplatin, and concomitant thoracic radiation in the treatment of advanced chest malignancies.

1998 ◽  
Vol 16 (6) ◽  
pp. 2157-2163 ◽  
Author(s):  
G A Masters ◽  
D J Haraf ◽  
P C Hoffman ◽  
L C Drinkard ◽  
S A Krauss ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Phase I Study ◽  
Maximum Tolerated Dose ◽  
Concurrent Chemotherapy ◽  
Unresectable Stage ◽  
Thoracic Radiation ◽  
Recommended Phase Ii Dose ◽  
Group B ◽  
Dose Levels

PURPOSE The cisplatin-vinorelbine regimen has superior activity in advanced non-small-cell lung cancer (NSCLC). We conducted a phase I trial to identify the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of this regimen with concomitant thoracic radiation (RT) in patients with advanced chest malignancies. PATIENTS AND METHODS Patients with advanced chest malignancies that required RT were enrolled onto this phase I study of standard chest radiation (30 daily 2-Gy fractions for a total of 60 Gy) and concurrent chemotherapy with cisplatin starting at 100 mg/m2 every 3 weeks and vinorelbine starting at 20 mg/m2/wk. RESULTS Thirty-seven patients were treated on this study. Two of three patients treated at the maximum-administered dose of cisplatin 100 mg/m2 per cycle and vinorelbine 25 mg/m2/wk experienced acute DLT (neutropenia), which required deescalation. The dose level of cisplatin 100 mg/m2 and vinorelbine 20 mg/m2/wk, although tolerated acutely, produced delayed esophagitis, which proved dose-limiting. The recommended phase II dose was cisplatin 80 mg/m2 every 3 weeks and vinorelbine 15 mg/m2 given 2 of every 3 weeks with concomitant chest RT. CONCLUSION Concomitant chemoradiotherapy with cisplatin and vinorelbine is feasible. The recommended phase II dose is cisplatin 80 mg/m2 every 3 weeks with vinorelbine 15 mg/m2 given twice over 3 weeks on a day 1/day 8 schedule. Esophagitis is the DLT, with neutropenia occurring at higher dose levels. A Cancer and Leukemia Group B (CALGB) phase II trial is currently underway to evaluate further the efficacy and toxicities of this regimen in unresectable stage III NSCLC.

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