A comparison of carboplatin plus methotrexate versus methotrexate alone in patients with recurrent and metastatic head and neck cancer.

1989 ◽  
Vol 7 (9) ◽  
pp. 1341-1345 ◽  
Author(s):  
M Eisenberger ◽  
S Krasnow ◽  
S Ellenberg ◽  
H Silva ◽  
J Abrams ◽  
...  
Keyword(s):  
Head And Neck ◽  
Ethical Issues ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Active Agent ◽  
Dose Schedule ◽  
Substantial Improvement ◽  
Two Stage ◽  
Study Objective

Patients with recurrent and metastatic squamous cell carcinoma of the head and neck (SCCHN) were stratified by performance status, extent of disease, and prior radiotherapy and subsequently randomized to receive carboplatin (CBDCA; Bristol-Myers, Wallingford, CT) administered intravenously (IV) monthly, initially at doses of 400 mg/m2 in combination with methotrexate (MTX) given IV weekly at doses of 40 mg/m2 or MTX alone at the same dose/schedule. Significant dose-limiting myelosuppression required CBDCA dose reductions to 300 mg/m2 and, subsequently, 200 mg/m2. Nonhematological toxicities were not significant. Our study objective was to determine whether CBDCA plus MTX produce a substantial improvement in response rate over single-agent MTX. A response rate of 50% (complete [CR] plus partial response [PR]) for CBDCA plus MTX compared with 25% for MTX was specified as the difference to be detected. We employed a two-stage study design for randomized trials that allowed for early termination of studies involving relatively ineffective treatment regimens. With this design, the study could be closed after the first stage (20 patients entered onto each treatment arm) if the number of responders to CBDCA plus MTX were not superior to MTX. Five of 20 patients responded to treatment in each arm, and we were able to conclude that the addition of CBDCA to MTX is unlikely to result in a twofold increase in response rate compared with MTX alone in this group of patients. This two-stage design represents a simple and efficient method of testing the relative efficacy of new combinations containing at least one active agent against a suitable control arm in this disease. It addresses scientific and ethical issues of continuing testing with relatively ineffective treatments, and at the same time provides a reliable method for identifying very active regimens likely to represent significant therapeutic advances.

Final results of a phase II study of erlotinib, docetaxel and cisplatin in patients with recurrent/metastatic head and neck cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6013-6013 ◽  
Author(s):  
E. S. Kim ◽  
M. S. Kies ◽  
B. S. Glisson ◽  
A. Tsao ◽  
L. E. Ginsberg ◽  
...  
Keyword(s):  
Growth Factor ◽  
Head And Neck ◽  
Response Rate ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Treatment Options ◽  
Single Agent ◽  
Progression Free Survival ◽  
Egfr Signaling Pathway ◽  
Grade 3

6013 Background: Interrupting the epidermal growth factor receptor (EGFR) signaling pathway has shown promise in a variety of cancers and preclinical data has demonstrated possible synergy with platinums and taxanes. Treatment options for recurrent/metastatic HNSCC are limited. A study of cisplatin and docetaxel showed a response rate of 40% and 9.6 month median survival. Erlotinib, an EGFR tyrosine kinase inhibitor, had a 4.3% response rate as single agent in HNSCC. Because of the possible synergy and efficacy, we proposed to study the combination of cisplatin, docetaxel and erlotinib in advanced HNSCC. Methods: Patients (pts) were required to have adequate performance status, measurable disease, no prior EGFR therapy, and may have received prior induction, concomitant or adjuvant chemotherapy, but not for recurrent/metastatic disease. Sites of disease included squamous cell head and neck sites excluding nasopharynx and sinus. Treatment included docetaxel 75 mg/m2 and cisplatin 75 mg/m2 intravenously every 3 weeks and erlotinib 150 mg by mouth daily. All agents were started on day 1. Pts were treated with growth factor support. Results: The trial has completed accrual to 50 pts. 47 pts are available for analysis at this time. Median age is 56 years (range 39–72). ECOG PS is 0, 1, 2 (6, 29, 2 pts). 43 pts are evaluable for efficacy. All responses were confirmed via RECIST. Complete responses have been in observed in 4 pts, partial responses in 25 pts and 12 pts have stable disease for an overall response rate of 67% and disease control rate of 95%. After a follow-up of 19 months, median overall survival was 11 months (8.61, 22.5, 95% CI) and progression free survival was 6.01 months (4.37, 8.25). 6 pts had grade 3/4 febrile neutropenia, 4 pts had grade 3/4 dehydration, 3 pts had grade 3 diarrhea, and 2 pts had grade 3/4 GI bleeding. The most common grade 1–2 toxicities were diarrhea, nausea, and rash. Conclusions: The combination of cisplatin, docetaxel and erlotinib is well tolerated and has very encouraging activity in recurrent/metastatic HNSCC. Tissues are being collected and analyzed for correlative markers including downstream EGFR pathway markers (p-akt, mek, k-ras). Final efficacy and biomarker results will be presented at the annual meeting. No significant financial relationships to disclose.

Phase II trial of vinorelbine in metastatic squamous cell esophageal carcinoma. European Organization for Research and Treatment of Cancer Gastrointestinal Treat Cancer Cooperative Group.

1996 ◽  
Vol 14 (1) ◽  
pp. 164-170 ◽  
Author(s):  
T Conroy ◽  
P L Etienne ◽  
A Adenis ◽  
D J Wagener ◽  
B Paillot ◽  
...  
Keyword(s):  
Esophageal Carcinoma ◽  
Squamous Cell ◽  
Response Rate ◽  
Single Agent ◽  
Active Agent ◽  
Dose Intensity ◽  
World Health ◽  
Who Grade ◽  
European Organization ◽  
Prior Chemotherapy

PURPOSE To evaluate the response rate and toxic effects of vinorelbine (VNB) administered as a single agent in metastatic squamous cell esophageal carcinoma. PATIENTS AND METHODS Forty-six eligible patients with measurable lesions were included and were stratified according to previous chemotherapy. Thirty patients without prior chemotherapy and 16 pretreated with cisplatin-based chemotherapy were assessable for toxicity and response. VNB was administered weekly as a 25-mg/m2 short intravenous (i.v.) infusion. RESULTS Six of 30 patients (20%) without prior chemotherapy achieved a partial response (PR) (95% confidence interval [CI], 8% to 39%). The median duration of response was 21 weeks (range, 17 to 28). One of 16 patients (6%) with prior chemotherapy had a complete response (CR) of 31 weeks' duration (95% CI, 0% to 30%). The overall response rate (World Health Organization [WHO] criteria) was 15% (CR, 2%; PR 13%; 95% CI, 6% to 29%). The median dose-intensity (DI) was 20 mg/m2/wk. VNB was well tolerated and zero instances of WHO grade 4 nonhematologic toxicity occurred. At least one episode of grade 3 or 4 granulocytopenia was seen in 59% of patients. A grade 2 or 3 infection occurred in 16% of patients, but no toxic deaths occurred. Other side effects were rare, and peripheral neurotoxicity has been minor (26% grade 1). CONCLUSION These data indicate that VNB is an active agent in metastatic esophageal squamous cell carcinoma. Given its excellent tolerance profile and low toxicity, further evaluation of VNB in combination therapy is warranted.

Phase II Trial of the Combination of Bevacizumab and Erlotinib in Patients Who Have Advanced Hepatocellular Carcinoma

2009 ◽  
Vol 27 (6) ◽  
pp. 843-850 ◽  
Author(s):  
Melanie B. Thomas ◽  
Jeffrey S. Morris ◽  
Romil Chadha ◽  
Michiko Iwasaki ◽  
Harmeet Kaur ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Response Rate ◽  
Group Performance ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Study Objective ◽  
Advanced Hcc

Purpose The study objective was to determine the proportion of patients with hepatocellular carcinoma (HCC) treated with the combination of bevacizumab (B) and erlotinib (E) who were alive and progression free at 16 weeks (16-week progression-free survival [PFS16]) of continuous therapy. Secondary objectives included response rate, median PFS, survival, and toxicity. Patients and Methods Patients who had advanced HCC that was not amenable to surgical or regional therapies, up to one prior systemic treatment; Childs-Pugh score A or B liver function; Eastern Cooperative Oncology Group performance status 0, 1, or 2 received B 10 mg/kg every 14 days and E 150 mg orally daily, continuously, for 28-day cycles. Tumor response was evaluated every 2 cycles by using Response Evaluation Criteria in Solid Tumors Group criteria. A total of 40 patients were treated. Results The primary end point of PFS16 was 62.5%. Ten patients achieved a partial response for a confirmed overall response rate (intent-to-treat) of 25%. The median PFSevent was 39 weeks (95% CI, 26 to 45 weeks; 9.0 months), and the median overall survival was 68 weeks (95% CI, 48 to 78 weeks; 15.65 months). Grades 3 to 4 drug-related toxicity included fatigue (n = 8; 20%), hypertension (n = 6; 15%), diarrhea (n = 4; 10%) elevated transaminases (n = 4; 10%), gastrointestinal hemorrhage (n = 5; 12.5%), wound infection (n = 2; 5%) thrombocytopenia (n = 1; 2.5%), and proteinuria, hyperbilirubinemia, back pain, hyperkalemia, and anorexia (n = 1 each). Conclusion The combination of B + E in patients who had advanced HCC showed significant, clinically meaningful antitumor activity. B + E warrant additional evaluation in randomized controlled trials.

Phase I study of the combination of fludarabine, mitoxantrone, and dexamethasone in low-grade lymphoma.

1994 ◽  
Vol 12 (3) ◽  
pp. 575-579 ◽  
Author(s):  
P McLaughlin ◽  
F B Hagemeister ◽  
F Swan ◽  
F Cabanillas ◽  
O Pate ◽  
...  
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Single Agent ◽  
Active Agent ◽  
Large Cell ◽  
Maximum Tolerated Dose ◽  
Low Grade ◽  
Overall Response ◽  
Nonhematologic Toxicity ◽  
High Fraction

PURPOSE Fludarabine is an active agent for patients with low-grade lymphoma (LGL) but has mainly been used as a single agent. This trial was designed to define the maximum-tolerated dose (MTD) of a combination of fludarabine, mitoxantrone, and dexamethasone (FND), to identify the toxicities of these agents in combination, and to make preliminary observations about the efficacy of this combination. PATIENTS AND METHODS Twenty-one patients with recurrent LGL or follicular large-cell lymphoma were treated, in cohorts of three, at stepwise escalating doses. Patients were required to have adequate marrow function and normal renal, hepatic, and cardiac function. RESULTS The MTD of the combination was found to be as follows: fludarabine, 25 mg/m2/d (days 1 to 3); mitoxantrone, 10 mg/m2 (day 1); and dexamethasone, 20 mg/d (days 1 to 5). Each course was administered monthly, and up to eight courses were given. Dose-limiting toxicities were neutropenia and infections. Thrombocytopenia was modest. Nonhematologic toxicity was very modest. Responses were seen at every dose level. The overall response rate was 71%, with a 43% complete remission (CR) rate. The median duration of CR was 18 months (with follow-up duration from 13 to 28+ months). CONCLUSION FND was well tolerated in this population. While our primary aim was to define the MTD, our preliminary observations on the efficacy of the regimen were favorable. The overall response rate was high, there was a high fraction of CRs, and our early impression is that these responses are durable.

Open-Label, Uncontrolled, Multicenter Phase II Study to Evaluate the Efficacy and Toxicity of Cetuximab As a Single Agent in Patients With Recurrent and/or Metastatic Squamous Cell Carcinoma of the Head and Neck Who Failed to Respond to Platinum-Based Therapy

2007 ◽  
Vol 25 (16) ◽  
pp. 2171-2177 ◽  
Author(s):  
Jan B. Vermorken ◽  
José Trigo ◽  
Ricardo Hitt ◽  
Piotr Koralewski ◽  
Eduardo Diaz-Rubio ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Combination Therapy ◽  
Disease Control ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Disease Progression ◽  
Response Rate ◽  
Single Agent ◽  
Open Label ◽  
Metastatic Squamous Cell Carcinoma

PurposeTo evaluate the efficacy and safety of the epidermal growth factor receptor–directed monoclonal antibody cetuximab administered as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) who experience disease progression on platinum therapy.Patients and MethodsAn open-label multicenter study in which patients with disease progression on two to six cycles of platinum therapy received single-agent cetuximab (initial dose 400 mg/m2followed by subsequent weekly doses of 250 mg/m2) for ≥ 6 weeks (single-agent phase). Patients who experienced disease progression could receive salvage therapy with cetuximab plus platinum (combination-therapy phase). From June 2001 to December 2002, 103 patients were enrolled and treated with cetuximab, 53 of whom subsequently received combination therapy.ResultsIn the single-agent phase, response rate was 13%, disease control rate (complete response/partial response/stable disease) was 46%, and median time to progression (TTP) was 70 days. During the combination-therapy phase, the objective response rate was zero, disease control rate was 26%, and TTP was 50 days. Median overall survival was 178 days. Treatment was well tolerated. The most common cetuximab-related adverse events in the single-agent phase were skin reactions, particularly rash (49% of patients, mainly grade 1 or 2). There was one treatment-related death due to an infusion-related reaction.ConclusionSingle-agent cetuximab was active and generally well tolerated in the treatment of recurrent and/or metastatic SCCHN that progressed on platinum therapy. Response was comparable to that seen with cetuximab plus platinum combination regimens in the same setting.

scholarly journals Phase III Randomized, Placebo-Controlled Trial of Docetaxel With or Without Gefitinib in Recurrent or Metastatic Head and Neck Cancer: An Eastern Cooperative Oncology Group Trial

2013 ◽  
Vol 31 (11) ◽  
pp. 1405-1414 ◽  
Author(s):  
Athanassios Argiris ◽  
Musie Ghebremichael ◽  
Jill Gilbert ◽  
Ju-Whei Lee ◽  
Kamakshi Sachidanandam ◽  
...  
Keyword(s):  
Head And Neck ◽  
Disease Progression ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Single Agent ◽  
Eastern Cooperative Oncology Group ◽  
Phase Iii ◽  
Oncology Group ◽  
Ecog Performance Status ◽  
Grade 3

Purpose We hypothesized that the addition of gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, to docetaxel would enhance therapeutic efficacy in squamous cell carcinoma of the head and neck (SCCHN). Patients and Methods Patients with recurrent or metastatic SCCHN with Eastern Cooperative Oncology Group (ECOG) performance status of 2, or patients with ECOG performance status of 0 to 2 but were previously treated with chemotherapy, were randomly assigned to receive weekly docetaxel plus either placebo (arm A) or gefitinib 250 mg/d, orally (arm B) until disease progression. At the time of progression, patients in the placebo arm could receive single-agent gefitinib. EGFR, c-MET, and KRAS mutations and polymorphisms in drug metabolizing enzymes and transporters were evaluated by pyrosequencing. Results Two hundred seventy patients were enrolled before the study was closed early at interim analysis (arm A, n = 136; arm B, n = 134). Median overall survival was 6.0 months in arm A versus 7.3 months in arm B (hazard ratio, 0.93; 95% CI, 0.72 to 1.21; P = .60). An unplanned subset analysis showed that gefitinib improved survival in patients younger than 65 years (median 7.6 v 5.2 months; P = .04). Also, there was a trend for improved survival in patients with c-MET wild-type (5.7 v 3.6 months; P = .09) regardless of treatment. Grade 3/4 toxicities were comparable between the two arms except that grade 3/4 diarrhea was more common with docetaxel/gefitinib. Of 18 eligible patients who received gefitinib after disease progression in arm A, one patient had a partial response. Conclusion The addition of gefitinib to docetaxel was well tolerated but did not improve outcomes in poor prognosis but otherwise unselected patients with SCCHN.

A Single-Center Study To Evaluate the Safety and Efficacy of Intravenous/Oral Fludarabine in Untreated Gastric MALT Lymphoma. Impact of t(11;18)(q21;q21) in Molecular Response Rates.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4439-4439
Author(s):  
Antonio Salar ◽  
Beatriz Bellosillo ◽  
Agustín Seoane ◽  
Luz Martinez ◽  
Ana Ferrer ◽  
...  
Keyword(s):  
Malt Lymphoma ◽  
Response Rate ◽  
Single Agent ◽  
Active Agent ◽  
Hematological Toxicity ◽  
Clinical Activity ◽  
Gastric Malt Lymphoma ◽  
Molecular Response ◽  
Sequencing Analysis

Abstract Background: The treatment of gastric mucosa-associated lymphoid tissue (MALT) lymphoma in the absence of H. pylori infection or when the lymphoma fails to regress after adequate antibiotic treatment remains controversial. Fludarabine (F) is an active agent for indolent lymphoma, however, its clinical activity in gastric MALT lymphoma has not been studied. The aim of the study is to assess the efficacy and safety of single-agent fludarabine in gastric MALT lymphoma and to analyze the molecular response (MR) after this treatment. Methods: Treatment consisted of fludarabine (25 mg/m2 IV) given on days 1–5, every 4 weeks, for 6 cycles; after the first cycle, oral fludarabine was allowed to be given orally at 40 mg/m2 with the same schedule. Molecular response (MR) was assessed by RT-PCR analysis of t(11;18) or by PCR assays for analysis of IgH gene rearrangements analyzing FR1, FR2 and FR3 in endoscopic biopsies. Results: Eight consecutive patients were included. Median age: 60 years (range: 45–77); 3 pts were in stage I, 2 stage II-1 and 3 stage IV according to Lugano system. Four out of 5 (80%) pts achieved a CR after three cycles and all eight cases (100%) achieved a CR after six cycles, for an overall response rate of 100%. After a median follow-up of 44 months (range 14.5–58 mo) no patient has shown clinical or endoscopic relapse. Hematological toxicity occurred in 75% of pts, mainly mild neutropenia and generally after the third cycle. Three cases received G-CSF (after the 2nd, 3rd and 6th cycle) and three patients required dose modification or delay (3–7 days) in the delivery of the following cycle. No blood transfusions were required. Only one patient had to be admitted because of non-neutropenic fever. None case of myelodisplasia has been detected at last follow-up. Four out of 8 pts (50%) achieved MR during the study-period (see figure). Four out of 5 (80%) pts without t(11;18) achieved MR. In contrast, no patient carrying t(11;18) achieved MR. Sequencing analysis of monoclonal PCR products will be presented. Conclusions: Fludarabine, either intravenous or oral, is safe and achieve a high response rate when given in gastric MALT lymphoma, with many pts achieving MR. In those pts carrying t(11;18), residual disease can be detected by PCR but do not determine relapse at present follow-up. Figure Figure

Clinical experience of using docetaxel-cisplatin in the treatment of advanced ovarian cancer: A Bangladesh perspective

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 15070-15070
Author(s):  
M. Mokhlesuddin ◽  
P. S. Akhter ◽  
D. U. Ahmed ◽  
M. A. Khan ◽  
M. A. Rahman ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Active Agent ◽  
Advanced Ovarian Cancer ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Advanced Epithelial Ovarian Cancer ◽  
Bangladeshi Population

15070 Background: Docetaxel is an active agent in the treatment of recurrent advanced ovarian cancer. We conducted a multi-center phase II study to evaluate the response rate, toxicity and survival of docetaxel-cisplatin regimen as first-line treatment of advanced ovarian cancer in Bangladeshi population. Methods: Forty chemotherapy-naïve patients of advanced epithelial ovarian cancer were recruited between October 1999 to March 2002. Eligibility criteria included stage Ic-IV patients, age 18–75 years, an ECOG performance status of 0–3 with adequate hepatic, renal and bone marrow function. Docetaxel 60 mg/m2 as 1 hour IV infusion and cisplatin 75 mg/m2 were given on day 1 every 3 weeks for a maximum of 6 cycles (average 5 cycles). Tumor responses and toxicities were evaluated by relevant investigations and survival was documented. Results: A total of 40 patients were enrolled. Median age was 44 years (age range 18–75 years). All the patients were evaluable for response. Overall response was observed in 32 patients (80%) with complete response rate 38% (12 patients), partial response rate 62% (20 patients). Stable disease was seen in 5 patients (12.5%) and progressive disease was in 3 patients (7.5%).Two years survival was documented in 62% patients. Toxicities were limited with grade 3 neutropenia in 10 patients (25%) and some non-hematological toxicities (including nausea, vomiting and fluid retention) in twenty-six patients (65%). No severe febrile neutropenia and no events of death were observed. Conclusions: The combination of docetaxel and cisplatin appears to be effective with manageable toxicities in patients with advanced epithelial ovarian cancer in Bangladeshi population. No significant financial relationships to disclose.

A combination chemotherapy of weekly paclitaxel and doxifluridine (5’-DFUR: an intermediate metabolite of capecitabine) in patients with unresectable or recurrent gastric cancer in an outpatient setting. Final results of a multicenter phase II trial

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15050-15050
Author(s):  
S. Yoshino ◽  
T. Nishimura ◽  
S. Hazama ◽  
M. Oka ◽  
H. Ozasa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Adverse Events ◽  
Phase Ii ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Outpatient Setting ◽  
Eligibility Criteria ◽  
Line Therapy ◽  
Recurrent Gastric Cancer

15050 Background: Paclitaxel (PTX) and 5’-DFUR have single-agent activity in gastric cancer and have distinct mechanisms of action and no overlap of key toxicities. Synergistic interaction between PTX and 5’-DFUR is mediated by taxane-induced up-regulation of thymidine phosphorylase, which converts 5’-DFUR to 5-FU. We conducted a combination phase II study of PTX and 5’-DFUR in patients with unresectable or recurrent gastric cancer to evaluate the efficacy and safety in an outpatient. Methods: Eligibility criteria included patients with histologically proven unresectable or recurrent gastric cancer who had measurable lesions fitting RECIST, up to one prior chemotherapy, a performance status of 0–2 and adequate organ function. According to our results of phase I study (Proc ASCO 2004, Abstr. 4228), the treatment included PTX 70 mg/m2 i.v. on days 1, 8, and 15 every 4 weeks and 5’-DFUR 600 mg/body p.o. everyday until there was disease progression or the appearance of unacceptable toxicity. Primary endpoint was: RR; and secondary endpoints were OS, PFS, TTF and onset rate of adverse events. Results: Between June 2004 and July 2006, 42 patients were enrolled in this study: including 34 men; 8 women; median age of 70 years (range, 44–85 years); and PS levels were, zero with 27, one with 13 and two with 2 patients. In 42 eligible patients, clinical usefulness was evaluated resulting in response rate of 40.5% (CR, 1; PR, 16; SD, 17; PD, 6; and NE, 2 patients). The first-line therapy involved 28 patients in whom the response rate was 50.0%. The second-line therapy involved 13 patients (all TS-1 failure) in whom the response rate was 23.1%. OS was 371 days, PFS was 170 days and TTF was 147 days. All patients were treated in outpatient. Severe adverse events were found in 2 patients to discontinue the present treatment, though other adverse events were relatively mild without death due to the present therapy. Commonly observed grade 3/4 adverse events were neutropenia (26.2%), appetite loss (4.8%), neuropathy (4.8%), and fatigue (4.8%). Conclusions: The outpatient combination of a weekly PTX and 5’-DFUR chemotherapy is active and well tolerated. No significant financial relationships to disclose.

Randomized phase II trial of docetaxel, with or without doxercalciferol, in advanced, androgen-independent prostate cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5119-5119
Author(s):  
S. Attia ◽  
J. Eickhoff ◽  
G. Wilding ◽  
J. Blank ◽  
H. Rezazadeh ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Vitamin D ◽  
Response Rate ◽  
Performance Status ◽  
Single Agent ◽  
Objective Response ◽  
Double Blind ◽  
Vitamin D Analogs ◽  
Psa Response ◽  
Androgen Independent

5119 Background: Docetaxel is the standard of care for advanced androgen-independent prostate cancer (AIPC). Doxercalciferol, a vitamin D analog (1a-hydroxyvitamin D2), has single-agent activity in AIPC (Clin Cancer Res 9(11), 2003). Preclinical evidence supports combining vitamin D with chemotherapy to treat AIPC. Here we report results of a multi-institutional trial combining docetaxel and doxercalciferol. Methods: Patients with chemo-naive AIPC were randomized 1:1 to receive, on a four week cycle, docetaxel (35 mg/m2 IV; days 1, 8 and 15) with either doxercalciferol (10 mcg PO daily, days 1–28) or placebo in a double-blind fashion. The primary endpoint was to compare progression-free survival (PFS). Secondary endpoints were to assess overall survival (OS), objective response (RECIST), PSA response (consensus criteria), and toxicity. PFS and OS were analyzed on an intent-to-treat basis. Eligibility criteria included no prior cytotoxic therapy; radiographic evidence of metastasis; performance status ≤ 2 and no recent history of nephrolithiasis. Results: Seventy patients were randomized. Median follow-up time was 16.2 months (range, 0–40.5 months). Median PFS in the doxercalciferol arm was 14.9 months (95% CI: 8.7–16.6 months) versus 11.9 months (95% CI: 8.9–16.4 months) in the placebo arm (p=0.73). Median OS in the doxercalciferol arm was 18.1 months (95% CI: 14.9–26.2 months) and 17.9 months (95% CI: 12.1–24.6 months) in the placebo arm (p=0.63). Twenty-nine patients in the doxercalciferol arm and 33 in the placebo arm were evaluable for objective response. No complete responses were seen. Partial response rate was 14% (doxercalciferol) vs. 15% (placebo) (p=0.88). PSA response rate was 44% (95% CI: 29%-60%) in the doxercalciferol arm and 42% (95% CI: 27%-59%) in the placebo arm (p=0.87). Grade 3/4 toxicity rates were 38% in the doxercalciferol arm and 39% in the placebo arm (p=0.99). Conclusions: Despite encouraging data with other vitamin D analogs combined with docetaxel in AIPC, the addition of daily doxercalciferol to weekly docetaxel did not enhance median PFS, OS or tumor response. Toxicity was similar between treatment groups. Further evaluation of vitamin D analogs in combination with chemotherapy in AIPC remains of interest. No significant financial relationships to disclose.

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