Negative Correlation between the Response Rate and the Response Duration during Punishment Condition in Rats

In this phase II multicenter trial, 67 evaluable patients with advanced measurable gastric carcinoma were treated with a combination of etoposide, Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), and cisplatin (EAP). The overall response rate was 64%, including 21% complete responses (CRs). In 55 patients with metastatic disease, 31 responses (51%) including eight CRs (15%) were achieved. Responses were seen in all metastatic sites, but the response rate was lower in patients with peritoneal carcinomatosis. In 12 patients with locoregional disease, six CRs and six partial responses (PRs) were observed. Eight CRs (three and five in patients with metastatic and locoregional disease, respectively) were pathologically confirmed. The overall median response duration was 7 months; it was 16 months for patients achieving CR (22 months for pathologically confirmed CR [pCR]), and 6 months for PR. The median survival time for all patients was 9 months, for the patients who achieved CR 17 months, for pCR 23 months, and for PR 9.5 months. Median survival time for all patients with metastatic disease was 8 months, and for locoregional disease 12.5 months. Six patients (9%) (four local, two metastatic disease) were alive at 2 years, and four patients are alive and disease free at 35+ to 56+ months. Main toxicities were leukopenia and thrombocytopenia, with 64% of patients developing grade 3 to 4 myelosuppression and 12% severe infections. Nonhematologic toxicities of World Health Organization (WHO) grade 4 were not observed.

Download Full-text

Phase II trial of docetaxel in advanced anthracycline-resistant or anthracenedione-resistant breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.1995.13.12.2879 ◽

1995 ◽

Vol 13 (12) ◽

pp. 2879-2885 ◽

Cited By ~ 233

Author(s):

P M Ravdin ◽

H A Burris ◽

G Cook ◽

P Eisenberg ◽

M Kane ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Response Rate ◽

Objective Response ◽

Metastatic Breast ◽

Response Duration ◽

Fluid Retention ◽

Skin Reactions ◽

Median Response ◽

High Level

PURPOSE The purpose of this study was to evaluate the clinical efficacy and safety of docetaxel in patients with metastatic breast cancer (MBC) resistant to doxorubicin or mitoxantrone. PATIENTS AND METHODS Docetaxel 100 mg/m2 was administered as a 1-hour intravenous (IV) infusion every 3 weeks to 42 patients registered at four centers. Patients must have received at least one but no more than two prior chemotherapy regimens for MBC (in addition to any prior adjuvant therapy). One of the regimens for metastatic breast cancer must have included an anthracycline or anthracenedione and the cancer must have progressed on that regimen. RESULTS Objective responses were seen in 20 of 35 assessable patients (three complete responses [CRs] and 17 partial responses [PRs]), for an objective response rate of 57% (95% confidence interval [CI], 39% to 74%) and in 21 of 42 registered patients (50% response rate [RR]; 95% CI, 34% to 66%) entered onto the trial. The median response duration was 28 weeks. The most common toxicity in this study was grade 4 neutropenia, which occurred in 95% of patients. Other clinically significant nonhematologic side effects included stomatitis, skin reactions, neurosensory changes, asthenia, and fluid retention. Patients who received dexamethasone premedication had a later onset of fluid retention than those who did not receive dexamethasone (onset at a median cumulative docetaxel dose of 503 mg/m2 and 291 mg/m2, respectively). CONCLUSION Docetaxel at this dose and schedule has a high level of antitumor activity in patients with treatment-refractory advanced breast cancer, and appears to be one of the most active agents for the treatment of this patient population.

Download Full-text

Calcitriol Elevation Is Associated with a Higher Risk of Refractory Hypercalcemia of Malignancy in Solid Tumors

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgz278 ◽

2019 ◽

Vol 105 (4) ◽

pp. e1115-e1123 ◽

Cited By ~ 1

Author(s):

Tariq Chukir ◽

Yi Liu ◽

Katherine Hoffman ◽

John P Bilezikian ◽

Azeez Farooki

Keyword(s):

Solid Tumors ◽

Negative Correlation ◽

Response Rate ◽

Retrospective Chart Review ◽

Significant Negative Correlation ◽

Hematologic Malignancies ◽

Antiresorptive Therapy ◽

Hypercalcemia Of Malignancy ◽

Metastatic Lesions ◽

Significant Difference

Abstract Background Hypercalcemia of malignancy (HCM) is a common complication of advanced cancer. PTH-independent HCM may be mediated through different mechanisms: (1) humoral HCM, caused by the secretion of PTH-related peptide (PTHrP), (2) local osteolysis resulting from metastatic lesions, and (3) calcitriol-mediated hypercalcemia. Calcitriol-mediated HCM in patients with nonlymphomatous solid tumors is thought to be rare. Methods We performed a retrospective chart review from 2008 to 2017 to characterize further patients at our institution with solid tumors who had HCM with concomitant elevations in calcitriol. Patients with PTH-dependent hypercalcemia and patients with evidence of granulomatous disease were excluded, as were patients with hematologic malignancies. We hypothesized that patients with HCM and elevated calcitriol levels would respond less favorably to treatment with antiresorptive therapy compared with patients with HCM but without calcitriol elevation. We also aimed to assess mortality and determine if PTHrP and phosphorus levels correlate with calcitriol because both factors may alter calcitriol levels. Results Of 101 eligible patients, calcitriol was elevated in 45 (45%). PTHrP was elevated in 76% of patients with elevated calcitriol compared with 52% of patients without calcitriol elevation. The mean PTHrP value did not differ between patients with HCM and elevated calcitriol (36.3 ± 22 pg/mL) and those without calcitriol elevation (37.4 ± 19 pg/mL). Those with elevated calcitriol levels generally did not respond completely to antiresorptive treatment (80% incomplete response rate), whereas most patients without an elevation in calcitriol responded well to antiresorptive treatment (78% response rate: P < .001). There was no significant difference in the percentage of patients with metastatic bone disease among the 2 groups (49% vs. 55%, respectively). There was no difference in mortality between the 2 groups (P = .14). A weak but significant negative correlation was found between phosphorus and calcitriol (Pearson r = -0.261, P = .016). This correlation was only significant in patients without calcitriol elevation (Pearson r = -0.4, P = .0082). Also, a significant negative correlation was found between PTHrP and phosphorus, again only in patients without calcitriol elevation. Discussion In the setting of HCM, patients with calcitriol elevation are much less likely to respond to antiresorptive therapy than patients without calcitriol elevation. Because calcitriol elevation did not appear to be correlated with hypophosphatemia or elevated PTHrP, it would appear that calcitriol production under these conditions is autonomous, and not subject to normal physiological controls. These observations indicate that calcitriol elevations in patients with HCM have clinical significance.

Download Full-text

Streptozocin plus fluorouracil versus doxorubicin therapy for metastatic carcinoid tumor.

Journal of Clinical Oncology ◽

10.1200/jco.1984.2.11.1255 ◽

1984 ◽

Vol 2 (11) ◽

pp. 1255-1259 ◽

Cited By ~ 181

Author(s):

P F Engstrom ◽

P T Lavin ◽

C G Moertel ◽

E Folsch ◽

H O Douglass

Keyword(s):

Heart Disease ◽

Carcinoid Tumor ◽

Response Rate ◽

Renal Toxicity ◽

Response Duration ◽

Hematologic Toxicity ◽

Metastatic Carcinoid ◽

Median Response ◽

Prior Chemotherapy ◽

Phase Ii And Iii

EST 5275 is a phase II and III study of fluorouracil plus streptozocin (5-FU plus STZ) or doxorubicin in patients with measurable progressive carcinoid tumor. Among one hundred seventy-two cases with no prior chemotherapy and no heart disease, the response rate was 22% for 5-FU plus STZ and 21% for doxorubicin, while the median response duration and median survival were 31 weeks and 64 weeks for the combination and 26 weeks and 48 weeks for doxorubicin. Thirty-three patients who failed 5-FU plus STZ crossed over to doxorubicin and achieved an 18% response. Of the thirty-five patients who failed on doxorubicin, 29% responded to 5-FU plus STZ. Hematologic toxicity was similar for both treatments; however, the 5-FU plus STZ patients experienced more vomiting but acceptable renal toxicity. Both chemotherapy regimens have antitumor activity in carcinoid tumors.

Download Full-text

Treatment of Myelodysplastic Syndromes with del 5q before the Lenalidomide Era: The GFM Experience.

Blood ◽

10.1182/blood.v108.11.2678.2678 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2678-2678 ◽

Cited By ~ 1

Author(s):

Charikleia Kelaidi ◽

Sophie Park ◽

Sabine Brechignac ◽

Lionel Mannone ◽

Norbert Vey ◽

...

Keyword(s):

Myelodysplastic Syndromes ◽

Response Rate ◽

Response Duration ◽

Response Rates ◽

Erythroid Response ◽

Recent Introduction ◽

Pre Treatment

Abstract Background: MDS with del 5q are characterized by profound anemia, which until the recent introduction of lenalidomide (N Engl J Med2005; 352: 549–57, J Clin Oncol2005;16S:5), was considered generally unresponsive to available treatments. In order to reevaluate the outcome of those patients in the pre-lenalidomide era, we analyzed response of anemia in MDS with del 5q treated with EPO ± G-CSF and thalidomide in previous GFM trials. Patients: MDS with del 5q included in 419 MDS treated with EPO or Darbepoetin (DAR) ± G-CSF by GFM centers (including 3 successive GFM trials: Blood2004; 104: 321–7; Blood2005;106 suppl 1: 712a; Br J Haematol2006;133: 513–9 and submitted to ASH 2006), and in 134 MDS treated with thalidomide in two successive GFM trials (Br J Haematol2005; 131: 609–18, and submitted to ASH 2006). Patients received at least 30,000 U/w of EPO or 300 mg/w of DAR and doses ranging from 50 to 800 mg/d of Thalidomide during at least 12 weeks. Results: 48 MDS with del 5q received EPO (or DAR) ± G-CSF, including 30 pts with del 5q alone, 9 with one and 9 with >1 additional cytogenetic abn; 21/48 had marrow blasts ≥5% (7 had >10%). 17 had the “5q- syndrome” according to WHO. Median pre-treatment EPO level was 287 UI/L (range 12–5,665), i.e. significantly more than in non del 5q cases (median 68, p<0.001). 22/48 pts (46%) had erythroid response, including 15 major and 7 minor (11 responses after EPO or DAR alone and 11 after EPO or DAR + G-CSF) vs. 64% in pts without del 5q (p=0.01) (p= 0.066 after adjustment for marrow blasts). The response rate was 52%, 55%, 22% and 33%, respectively in del 5q pts with the 5q- syndrome, one additional cytogenetic abn, >1 additional cytogenetic abn, and marrow blasts ≥5%. Response duration was significantly shorter in MDS with del 5q than in other MDS (mean 12 vs. 24 months, p=0.019) and in pts with 5q- syndrome vs. other MDS with marrow blasts <5% (mean 11vs. 24months, p=0.025). 20 pts with del 5q were treated with thalidomide. 6/20 had an erythroid response (30 %, including 3 major and 3 minor responses) vs. 29% of other MDS (p=NS) Conclusion: MDS with del 5q with ≤1 additional cytogenetic abn and no excess of marrow blasts may have erythroid response to EPO ± G-CSF but responses are generally very short, while response rates to thalidomide are low. Those results are clearly inferior to results obtained with lenalidomide in MDS with del 5q.

Download Full-text

5-Azacytidine in 82 Low/Intermediate-1 IPSS Risk Myelodysplastic Syndromes: Results from the Italian Patient Named Program

Blood ◽

10.1182/blood.v112.11.2680.2680 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2680-2680

Author(s):

Pellegrino Musto ◽

Luca Maurillo ◽

Alessandra Spagnoli ◽

Antonella Gozzini ◽

Flavia Rivellini ◽

...

Keyword(s):

Overall Survival ◽

Myelodysplastic Syndromes ◽

Response Rate ◽

Previous Treatment ◽

Response Duration ◽

Complete Response ◽

Median Number ◽

Phase Iii ◽

Fixed Dose ◽

Female Ratio

Abstract 5-azacytidine (AZA) significantly prolonged overall survival in higher-risk patients with myelodysplastic syndromes (MDS) in a large, international, randomized, phase III trial (AZA-001). However, data about efficacy and safety of AZA in lower risk MDS are less consistent and only few small studies have addressed this topic. Among a total of 246 MDS treated with AZA in 31 different Italian Institutions since 2005 within to a national patient named program, we evaluated 82 patients scored as low/int-1 IPSS risk MDS. Median age was 68 years (range 34–85), male/female ratio 50/32. According to WHO classification, there were 21 RA/RARS, 4 5q-syndromes, 20 RCMD, 24 RAEB-1, 5 RAEB-2, 4 CMMoL, and 4 MDS unclassified. Median time from diagnosis was 27 months (range 1–132). Sixty-eight patients (82.9%) were transfusion-dependent, sixty (74%) had received a prior treatment, mostly with erythropoiesis stimulating agents. AZA was administered as single drug in 61 patients (74.4%), while in the remaining subjects it was variously combined with growth factors, valproic acid or other agents. Forty-eight patients (58.5%) received a “standard” AZA dose of 75 mg/sqm/d s.c., thirty-four (41.5%) a fixed dose of 100 mg/d s.c. Single cycle treatment duration was 7 days in 45 patients (54.9%), < 7 days in 32 patients (39%), > 7 days in 3 patients (3.7%), unknown in 2 patients (2.4%). The median number of monthly cycles was 6 (range 1–21), and 63 patients (76.8%) completed at least 4 cycles. The most relevant toxicities observed (grade 3–4) were represented by myelosuppression (22%) and infections (6%). According to 2006-updated IWG criteria, overall response rate was 39% (47.5% in patients who had completed at least 4 cycles). In particular, complete response, partial response and hematological improvement occurred in 12.2%, 8.5% and 18.3% of patients (15.8%, 11.1% and 20.6% in those who were treated with at least 4 cycles), respectively. Stable or progressive disease was observed in 29.3%/25.6% and 30.2%/22.2% of patients receiving less than or at least 4 cycles, respectively. Response duration ranged from 1 to +21 months. There were no significant differences in response rate according to dose and schedule employed, although a slight trend in favour of 75 mg/sqm vs 100 mg fixed dose was seen (45.8% vs 29.4%, respectively). There was also no difference in the percentages of response according to age, previous treatment and transfusion dependence. Overall survival at 2 years was 62%. A survival benefit emerged for responding patients, compared to non responders (82% vs 57%) (p=0.015). A favourable trend was also observed for transfusion-independent patients, while age, pre-treatment and AZA dose did not influence survival. These data indicate that AZA may be safe and effective for a subset of patients with low/int-1 IPSS risk MDS, resistant or not suitable for alternative treatments. The efficacy may improve if at least 4 cycles are administered.

Download Full-text

Long-term safety and efficacy of pomalidomide (POM) with or without low-dose dexamethasone (LoDEX) in relapsed and refractory multiple myeloma (RRMM) patients enrolled in the MM-002 phase II trial.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.8588 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 8588-8588 ◽

Cited By ~ 1

Author(s):

David Samuel DiCapua Siegel ◽

Paul Gerard Guy Richardson ◽

Ravi Vij ◽

Craig C. Hofmeister ◽

Rachid C. Baz ◽

...

Keyword(s):

Phase Ii ◽

Response Rate ◽

Phase Ii Trial ◽

Progression Free Survival ◽

Response Duration ◽

Median Number ◽

Open Label ◽

Safety And Efficacy ◽

Vein Thrombosis ◽

Intent To Treat

8588 Background: MM-002 is a randomized, open-label, multicenter phase II trial evaluating the safety and efficacy of POM with or without LoDEX in advanced RRMM pts. Methods: Pts who had received ≥ 2 prior therapies, including lenalidomide (LEN) and bortezomib (BORT), and were refractory to their last treatment were randomized to POM+LoDEX (POM 4 mg/day, days 1–21 of a 28-day cycle; LoDEX 40 mg/week) or POM alone. End points included progression-free survival (PFS), response rate (according to EBMT criteria and investigator assessment), response duration, overall survival (OS), and safety. The efficacy outcomes are based on the intent-to-treat population (POM+LoDEX, n = 113; POM, n = 108). Results: The median number of prior therapies in each group was 5 (range 1–13). In the POM+LoDEX arm, 30 (27%) pts had high-risk cytogenetics, including del(17p13) and/or t(4p16/14q32). The overall response rate (≥ partial response) was 34% and 15% with POM+LoDEX and POM, respectively, with a median duration of 8.3 (95% CI: 5.8–10.1) and 8.8 (95% CI: 5.5–11.4) mos, respectively. At least minimal response was observed in 45% and 31% of pts, respectively. Median PFS was 4.6 (95% CI: 3.6–5.5) and 2.6 (95% CI: 1.9–2.8) mos with POM+LoDEX and POM, respectively, with a median follow-up of 16.0 and 12.2 mos. Median OS was 16.5 (95% CI: 12.4–18.5) and 13.6 (95% CI: 9.6–18.1) mos, respectively. The most common treatment emergent Gr 3/4 adverse events (AEs) reported in the safety population (n = 219) were neutropenia (44%), anemia (23%), thrombocytopenia (21%), and pneumonia (18%); there were no reports of Gr 3/4 peripheral neuropathy. The incidence of deep-vein thrombosis was low (2%). AEs were managed through dose reductions or interruptions, and supportive care with G-CSF (52%), RBC transfusions (47%), and platelet transfusions (17%). Discontinuations due to AEs were 10%. Conclusions: POM with or without LoDEX is clinically effective and generally well tolerated in RRMM pts who have received multiple prior treatments, including LEN and BORT. AEs were predictable and manageable. Updated data will be presented at the meeting. Clinical trial information: NCT00833833.

Download Full-text

Carboplatin-based sequential chemotherapy for aged patients with advanced bladder cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.7_suppl.342 ◽

2015 ◽

Vol 33 (7_suppl) ◽

pp. 342-342

Author(s):

Takahiro Yoneyama ◽

Yuki Tobisawa ◽

Tohru Yoneyama ◽

Hayato Yamamoto ◽

Atsushi Imai ◽

...

Keyword(s):

Bladder Cancer ◽

Response Rate ◽

Response Duration ◽

First Line ◽

Sequential Chemotherapy ◽

Aged Patients ◽

Limited Effectiveness ◽

Advanced Bladder Cancer ◽

Grade 3 ◽

Carboplatin Auc

342 Background: We retrospectively evaluated the feasibility and effectiveness of carboplatin based chemotherapy for the patients 65 years or older with advanced bladder cancer. Methods: We treated 86 patients with advanced bladder cancer at our clinic between August 2004 and June 2014. 56 patients (40 men and 16 women) with the age of 65 years or older were enrolled. Their average age was 75.8 years old (65–86), average Ccr was 54.4 ml/min (14.5–113.0), and an average follow-up period was 21.7 months (2–81). There were 18 recurrent cases after radical surgery and 38 inoperable cases. The therapeutic regimen consisted of 2 lines: gemcitabine/carboplatin (GCarbo) therapy as the first line, with two courses as a set; GCarbo/docetaxel (GCarboD) therapy as the second line if the response in the first line was insufficient. GCarbo consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. If this regimen was effective, another 2 courses of GCarbo was performed. If this regimen did not induce any tumor size reduction, we switched to GCarboD, which consisted of 800mg/m2 gemcitabine on days 1 and 8, 70mg/m2 docetaxel on day 1, and carboplatin(AUC 3) on day 2. Treatment efficacy was checked every 2 course. Results: Of the 56 subjects who had undergone the GCarbo therapy, the response rate was 37.5% (CR+PR) with 4 and 17 subjects exhibiting CR and a PR, respectively; the average response duration was 10.0 months (2–78). The response rates of 12 instances of GCardoD was25.0 %; the overall median survival was 14.0 months throughout the carboplatin-based sequential chemotherapy. Adverse events (AE) of grade 3 or higher occurred in 33 of those who had undergone the GCarbo therapy (58.9%). In GCarboD regimen, there were 11 (91.7 %) of G3/4 AEs. Conclusions: Although the present study is small and preliminary, the present carboplatin-based sequential chemotherapy is safe and active for advanced bladder cancer of the patients 65 years or older. GCarbo regimen achieved acceptable response rate (37.5%) in advanced bladder cancer. The median overall survival of 14.0 months is acceptable when average age of 75.8 year for the subjects is took into consideration. However, GCardoD had limited effectiveness for non-responder of GCarbo.

Download Full-text

Carboplatin-based sequential chemotherapy for advanced bladder cancer patient with impaired renal function.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.2_suppl.401 ◽

2016 ◽

Vol 34 (2_suppl) ◽

pp. 401-401

Author(s):

Takahiro Yoneyama ◽

Jotaro Mikami ◽

Naoki Fujita ◽

Tendo Sato ◽

Yuta Kojima ◽

...

Keyword(s):

Bladder Cancer ◽

Renal Function ◽

Impaired Renal Function ◽

Response Rate ◽

Response Duration ◽

Bladder Cancer Patient ◽

First Line ◽

Sequential Chemotherapy ◽

Advanced Bladder Cancer ◽

Carboplatin Auc

401 Background: We retrospectively evaluated the feasibility and effectiveness of a caboplatin-based sequential chemotherapy for the patients with advanced bladder cancer whose creatinine clearance (Ccr) was 60 ml/min or below. Methods: We treated 68 patients with advanced bladder cancer at our clinic between August 2004 and December 2014. 48 patients with advanced bladder cancer (33 men and 15 women) whose Ccr were 60 ml/min or below were enrolled. Their average age was 72.5 years old (43–83), average Ccr of 43.3 ml/min (14.5–57.0), and an average follow-up period of 24.5 months (5–92). The therapeutic regimen consisted of 2 lines: gemcitabine/carboplatin (GCarbo) therapy as the first line, with two courses as a set; GCarbo/docetaxel (GCarboD) therapy as the second line if the response in the first line was insufficient. GCarbo consisted of 800mg/m2 gemcitabine on days 1, 8, and 15 and carboplatin (AUC 4) on day 2. If this regimen was effective, another 2 courses of GCarbo was performed. If this regimen did not induce any tumor size reduction, we switched to GCarboD, which consisted of 800mg/m2 gemcitabine on days 1 and 8, 70mg/m2 docetaxel on day 1, and carboplatin (AUC 3) on day 2. Results: Of the 48 subjects who had undergone the GCarbo therapy, the response rate was 35.4% (CR+PR) with 3 and 14 subjects exhibiting complete response (CR) and apartial response (PR), respectively; the average response duration was 10.8 months (2–90). The response rates of 9 instances of GCardoD was 33.3%; the overall median survival was 18.0 months throughout the sequential chemotherapy. Adverse events (AE) of grade 3 or higher occurred in 30 of those who had undergone the GCarbo therapy (62.5%). Conclusions: Although the present study is small and preliminary, the present carboplatin-based sequential chemotherapy is safe and active for advanced bladder cancer with impaired renal function. GCarbo regimen achieved acceptable response rate (35.4%) in advanced bladder cancer. The median overall survival of 18.0 months is acceptable when average Ccr of 43.3 ml/min for the subjects is took into consideration.

Download Full-text

Fluorouracil, Doxorubicin, and Streptozocin in the Treatment of Patients With Locally Advanced and Metastatic Pancreatic Endocrine Carcinomas

Journal of Clinical Oncology ◽

10.1200/jco.2004.04.024 ◽

2004 ◽

Vol 22 (23) ◽

pp. 4762-4771 ◽

Cited By ~ 383

Author(s):

Maria A. Kouvaraki ◽

Jaffer A. Ajani ◽

Paulo Hoff ◽

Robert Wolff ◽

Douglas B. Evans ◽

...

Keyword(s):

Response Rate ◽

Objective Response ◽

Locally Advanced ◽

Evaluation Criteria ◽

Progression Free Survival ◽

Response Duration ◽

Response To Treatment ◽

Rank Test ◽

Median Response ◽

Log Rank Test

Purpose The role of systemic chemotherapy in the management of pancreatic endocrine carcinoma (islet cell carcinoma; PEC) is an area of considerable controversy. Response rates ranging from 6% to 69% have been reported for streptozocin-based chemotherapy. We retrospectively studied 84 patients with locally advanced or metastatic PEC who had been treated with fluorouracil, doxorubicin, and streptozocin (FAS) to determine the objective response rate, duration of progression-free survival (PFS), and duration of overall survival (OS). Patients and Methods Eligible patients had histologic or cytologic confirmation of their tumor and measurable disease on computed tomography or magnetic resonance imaging scans. Response to treatment was evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors Committee. Results Sixty-one of the patients were male and 23 were female, with a median age of 54 years (range, 24 to 78 years). The response rate (RR) to FAS was 39%, with a median response duration of 9.3 months. The 2-year PFS rate was 41%, and the 2-year OS rate was 74%. The extent of liver metastatic disease correlated with a worse PFS (P = .01 by log-rank test) and a worse OS (P < .0001 by log-rank test). Analyses showed that metastatic replacement of more than 75% of the liver and prior chemotherapy were independently associated with inferior PFS. Conclusion Patients with locally advanced or metastatic PEC who are treated with FAS may have a reasonable RR, and responders may experience longer PFS and OS. The volume of metastases in the liver is the most important predictor of outcome.

Download Full-text