Gemcitabine And Cisplatin Chemotherapy Research Articles

Early outcome results of a phase I/II study for an IL-2/T-cell receptor fusion protein in combination with gemcitabine and cisplatin (GC) in patients with locally advanced or metastatic urothelial cancer.

e15010 Background: ALT-801 is a human IL-2/single-chain T-cell receptor fusion protein previously tested in a phase 1 in patients with advanced malignancy (Fishman 2011 CCR 17:7765) (CA097550). In various murine models, ALT-801 demonstrated potent activity against syngeneic and xenograft UC, suggesting sensitivity of this disease to IL-2 based immunotherapy (Wong, unpubl. data.). Although UC are sensitive to platinum-based chemotherapy, combinations such as gemcitabine (G) + cisplatin (C) are associated with CR rates of around 15%, and limited durability of responses with limited effects of retreatment. Methods: We report here initial efficacy results of co-administration of G (1000 mg/m2/dose, d 1 & 8), C (70 mg/m2/dose, d 1) and ALT-801 (escalating doses, d 3, 5, 8, 10) on a 21 day schedule, for 3 cycles, in patients with UC that was locally advanced, or metastatic, for whom GC chemotherapy would be considered. ALT-801 planned doses are 0.04 to 0.12 mg/kg/dose in 5 dose cohorts with a 3+3 escalation design. Subjects with at least stable disease after 3 courses may receive 4 additional weekly doses of ALT-801 alone. Results: To date, three Stage IV UC patients (1F, 2M; 59-63 yrs; 2 patients had predominantly nodal metastases and one patient liver metastases) completed treatment with 0.04 mg/kg ALT-801+GC. Two had previously undergone radical cystectomy and had then later failed following GC treatment. Grade 3/4 toxicities observed include neutropenia (2), thrombocytopenia (2), leukopenia (1), lymphopenia (1) and anemia (1), consistent with GC and ALT-801 known pharmacodynamic effects. All 3 had radiological CRs by week 13. One patient underwent radical cystectomy had a pCR. The next (0.06 mg/kg/dose) cohort has started treatment. A phase II expansion cohort is planned at the MTD. Conclusions: The early response pattern is encouraging in that ALT-801 may be a novel, active immunotherapy for UC. NCT01326871

First-SIGNAL: First-Line Single-Agent Iressa Versus Gemcitabine and Cisplatin Trial in Never-Smokers With Adenocarcinoma of the Lung

Gefitinib has shown high response rate and improved progression-free survival (PFS) in never-smokers with lung adenocarcinoma (NSLAs). We compared efficacy of gefitinib with gemcitabine and cisplatin (GP) chemotherapy in this group of patients as first-line therapy. In this randomized phase III trial, a total of 313 Korean never-smokers with stage IIIB or IV lung adenocarcinoma, Eastern Cooperative Oncology Group performance status 0 to 2, and adequate organ function were randomly assigned to receive either gefitinib (250 mg daily) or GP chemotherapy (gemcitabine 1,250 mg/m(2) on days 1 and 8; cisplatin 80 mg/m(2) on day 1 every 3 weeks, for up to nine courses). The primary objective was to demonstrate better overall survival (OS) for gefitinib compared with GP in chemotherapy-naive NSLAs. Three hundred nine patients were analyzed per protocol (gefitinib arm, n = 159; GP arm, n = 150). Gefitinib did not show better OS compared with GP (hazard ratio [HR], 0.932; 95% CI, 0.716 to 1.213; P = .604; median OS, 22.3 v 22.9 months, respectively). The 1-year PFS rates were 16.7% with gefitinib and 2.8% with GP (HR, 1.198; 95% CI, 0.944 to 1.520). Response rates were 55% with gefitinib and 46% with GP (P = .101). Myelosuppression, renal insufficiency, and fatigue were more common in the GP arm, but skin toxicities and liver dysfunction were more common in the gefitinib arm. Two patients (1.3%) in the gefitinib arm developed interstitial lung disease and died. Gefitinib failed to demonstrate superior OS compared with GP as first-line therapy for NSLAs.

Autologous Cytokine-induced Killer Cell Transfusion in Combination With Gemcitabine Plus Cisplatin Regimen Chemotherapy for Metastatic Nasopharyngeal Carcinoma

In this study, we evaluate the efficacy of autologous cytokine-induced killer cells (CIK) transfusion used in combination with gemcitabine and cisplatin (GC) chemotherapy to treat nasopharyngeal carcinoma in patients with distant metastasis after radiotherapy. From September 2007 to August 2008, 60 patients with distant metastasis after radiotherapy were followed up and were randomly divided into 2 groups. The 30 patients in the GC+CIK group were treated with adoptive autologous CIK cell transfusion in combination with GC chemotherapy; the 30 patients in the GC group were treated with chemotherapy alone. Short-term efficacy evaluation revealed that in the GC+CIK group, there were 3 cases of complete remission, 18 cases of partial remission, 2 cases of stabilization of disease, and 7 cases of progression of disease and the total effective rate was 70% (21/30). In the GC group, there were 0 cases of complete remission, 14 cases of partial remission, 3 case of stable disease, and 13 cases of progressive disease and the total effective rate was 46.7% (14/21). Kaplan-Meier survival analysis showed that the overall survival of the GC+CIK group was higher than that of the GC group, but the difference was not significant (P=0.1374, log-rank test). However, the progression-free survival of the GC+CIK group was significantly higher than that of the GC group (P=0.0234, log-rank test). Thus, our study indicated that CIK cell transfusion therapy used in combination with GC chemotherapy may be a more effective treatment for postradiotherapy distant metastasis of nasopharyngeal carcinoma patients.

Two cases of plasmacytoid variant of urothelial carcinoma of urinary bladder: systemic chemotherapy might be of benefit

We report two cases of the plasmacytoid variant of urothelial carcinoma of urinary bladder in which systemic chemotherapy was effective. In the first case, a 76-year-old man presented with dysphasia. Magnetic resonance imaging (MRI) and computed tomography revealed a brain tumor and a bladder tumor. Resection of the brain tumor and transurethral resection of the bladder tumor were performed. The pathological diagnosis was plasmacytoid variant of urothelial carcinoma of urinary bladder with brain metastasis (pT1N0M1). Three cycles of adjuvant MVAC (methotrexate, vinblastine, adriamycin, and cisplatin) chemotherapy were performed. He has no evidence of recurrence 96 months after resection of brain metastasis. In the second case, a 76-year-old man presented with hematuria. MRI revealed a bladder tumor with abdominal wall invasion, and a transurethral biopsy was performed. The pathological diagnosis was plasmacytoid variant of urothelial carcinoma of urinary bladder (cT4bN0M0). After three cycles of neoadjuvant GC (gemcitabine and cisplatin) chemotherapy, MRI demonstrated a complete response. Radical cystectomy was performed, and the pathological diagnosis was pT0pN0. Although there was no evidence of recurrence 9 months after radical cystectomy, he died from other causes. Our two cases suggest that systemic chemotherapy might be effective for the plasmacytoid variant of urothelial carcinoma.

Efficacy of Adjuvant Gemcitabine-Cisplatin Chemotherapy: A Comparative Study between Locally Advanced Transitional Cell Carcinoma of the Bladder and Upper Urinary Tract

Objective: To evaluate the comparative efficacy of adjuvant gemcitabine and cisplatin (GC) chemotherapy between patients with locally advanced transitional cell carcinoma (TCC) of the bladder and upper urinary tract. Patients and Methods: From 2001 to 2005, we retrospectively selected a total of 64 patients with locally advanced TCC of the bladder and upper urinary tract who received at least 3 cycles of adjuvant GC chemotherapy. We compared disease-free and overall survival between the 2 groups. Results: The recurrence rate was 30.3% in TCC of the bladder and 25.8% of the upper urinary tract (p = 0.633). Statistical analysis revealed that there was no significant difference in the disease-free or overall survival rate between TCC of the bladder and upper urinary tract treated with adjuvant GC chemotherapy. Conclusion: Under the circumstances of limited data about TCC of the upper urinary tract, this study may suggest that adjuvant GC chemotherapy in locally advanced TCC of the upper urinary tract is as effective as those of bladder.

集学的治療が奏効し，長期間良好なＱＯＬを維持している尿管癌・肝／リンパ節転移の１例

A 56-year-old man presented with asymptomatic gross hematuria. Computed tomography (CT) scan revealed right hydronephrosis and a slightly enhanced invasive tumor in the right lower ureter, providing a diagnosis of ureteral cancer stage cT3NOM0. The patient underwent minimum incision endoscopic nephrouretectomy, and pathological examination of the resected specimen revealed urothelial carcinoma and squamous cell carcinoma with metastases to right obturator lymph nodes (pT3pN2). Ten months later, CT scan of the abdomen revealed two hepatic metastases. After three courses of combination chemotherapy consisting of gemcitabine and cisplatin (GC), one tumor completely disappeared and another achieved a partial response. The patient underwent radiofrequency ablation (RFA) for the residual followed by GC chemotherapy. However, eighteen months later, CT scan of the abdomen revealed two metastatic foci in other hepatic lesion. The patient underwent RFA again followed by GC chemotherapy and then all hepatic metastases have not revealed enlargement. More than three years after surgery, the patient has achieved a high quality of life.

Methotrexate, vinblastine, doxorubicin and cisplatin combination regimen as salvage chemotherapy for patients with advanced or metastatic transitional cell carcinoma after failure of gemcitabine and cisplatin chemotherapy

We investigated the safety and efficacy of a methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) combination regimen as second-line chemotherapy for patients with advanced or metastatic transitional cell carcinoma who failed first-line gemcitabine and cisplatin (GC) chemotherapy. Thirty patients who had progressed or relapsed after GC chemotherapy as first-line treatment were enrolled in this study. The major toxicities were neutropaenia and thrombocytopaenia. A grade 3 or 4 neutropaenia occurred in 19 (63.3%) and a grade 3 or 4 thrombocytopaenia developed in nine patients (30.0%). There were no life-threatening complications during the study. The overall response was 30%. A complete response was achieved in two patients (6.7%) and a partial response in seven (23.3%). The overall disease control rate was 50%. Seven out of 16 patients who had responded previously to GC responded to M-VAC, while 2 out of 14 who had not responded to GC responded to M-VAC. The median response duration was 3.9 months and the median progression-free survival was 5.3 months. The median overall survival was 10.9 months. M-VAC showed encouraging efficacy and reversible toxicities in patients who had progressed after GC chemotherapy and, especially, M-VAC appears to be a reasonable option as a sequential treatment regimen in patients who responded previously to GC chemotherapy.

The Comparison of the Efficacy and Side Effects between M-VAC and GC Chemotherapy for Advanced or Metastatic Urothelial Carcinoma Patients with a Good Performance Status

Purpose: We wanted to compare the efficacy and toxicity of chemotherapy with methotrexate, vinblastine, adriamycin, cisplatin (M-VAC) versus gemcitabine and cisplatin (GC) for patients with advanced or metastatic urothelial carcinoma. Materials and Methods: Forty-nine patients diagnosed with advanced urothelial cell carcinoma and who were started on chemotherapy were divided into two groups. All of them had a 0-1 Eastern Cooperative Oncology Group performance status. 19 patients received M-VAC chemotherapy and 30 patients received the GC regimen. Among them, the subjects who completed more than 3 cycles of their recommended formula (13/19 for M-VAC, 28/30 for GC) were included in this study. They were evaluated for their overall response rate, the 5-year survival rate, toxicities and the drop-out rate. Results: The overall response rate and median survival period of the M-VAC and G-C groups were 38% (5/13 cases) and 46% (13/28 cases), and 16.7 months and 43.9 months, respectively. The 5-year survival rates in the two groups were 10% in the M-VAC group and 46% in the G-C treated group (p=0.013). The main hematologic complication was leukopenia and this occurred in 10/19 patients and more than grade 3 leukopenia was noted in 4/10 patients in the M-VAC group and in 19/30 patients and more than grade 3 was noted in 10/19 patients in the GC group. The common non-hematologic side effects between the two groups were nausea/vomiting (84.2% vs 47.7%), alopecia (47.4% vs 26.7%), diarrhea (15.8% vs 16.7%), and nephrotoxicity (15.8% vs 6.7%), respectively. The drop-out rates were 31.6% in the M-VAC group and 6.7% with the GC group. Conclusions: For patients with a good performance status with advanced or metastatic urothelial carcinoma, GC chemotherapy is more effective and it has more tolerable toxicities than does the M-VAC regimen. (Korean J Urol 2007;48:1229-1235) 󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏󰠏

Combination of gemcitabine and cisplatin (GC) chemotherapy for advanced or recurrent nasopharyngeal cancer (NPC): A phase II study

5577 Background : Combination of GC chemotherapy is active and has a favorable safety profile in some several solid tumors, including advanced squamous cell head and neck cancers. We evaluated the efficacy and toxicity of this combination in advanced or recurrent NPC. Methods : In a two-center phase II study, patients with histologically confirmed advanced or recurrent NPC, measurable disease, WHO PS 0–2, age 19–70 years, adequate organ function, and written informed consent, were treated with Gemcitabine 1250 mg/m2 day 1 and day 8; Cisplatin 80 mg/m2 day 1 every 3 weeks. Primary endpoint was objective response rate. Results : Thirty five patients were enrolled between 12/01 and 11/03. There were 27 male and 8 female, 33 with Javanese ethnicity and 2 Caucasian;. with a mean age was 45 years (19–68). All but 3 patients (91.4%) had undifferentiated histology. Twenty-two patients had metastatic or recurrent disease, 13 patients had locally advanced disease. All patients were chemonaive, and 10 patients had recurrent disease after radiotherapy. There were 2 complete responses and 22 partial responses, yielding an 83% overall response rate from in 29 evaluable patients (95 CI, 68% - 97%). Grade 4 liver toxicity was found in 2 of 166 (1.2%) cycles analyzed. Grade III/IV anemia, neutropenia and thrombocytopenia were found in 1.8%, 8.2% and 1.2% of cycles respectively. Two patients are still on treatment. With a median follow-up of 9 months (1–21), the median progression-free survival and overall survival are 9 and 19 months, respectively. Conclusion : Gemcitabine and cisplatin combination is effective and has a safe toxicity profile for advanced and recurrent NPC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Elli Lily

Gemcitabine and cisplatin (GC) +/− subsequent maintenance therapy with single-agent gemcitabine in advanced non-small cell lung cancer (NSCLC): Preliminary results of a randomized trial of the Central European Cooperative Oncology Group (CECOG)

7067 Background: The optimal treatment duration for NSCLC patients is still a matter of discussion. Objectives of this trial were to compare time to progressive disease (TTPD) in patients treated with single-agent gemcitabine maintenance therapy plus best supportive care (BSC) versus BSC alone following standard GC therapy, to record responses in both arms, and to compare toxicity, duration of response, and overall survival. Methods: Chemonaive patients with stage IIIB or IV NSCLC, no prior radiotherapy >60 Gy to the chest, and a Karnofsky performance status (KPS) of ≥70 received 4 cycles of gemcitabine 1250 mg/m2 (days 1 and 8) plus cisplatin 80 mg/m2 (day 1). At the end of cycle 4, patients without progressive disease (PD) per SWOG criteria were randomized to gemcitabine 1250 mg/m2 (days 1 and 8) maintenance therapy until PD plus BSC (arm A) or BSC only (arm B) in a 2:1 fashion. Radiotherapy was not permitted on both arms. Cycles were repeated every 21 days. Time-to-event endpoints were calculated using the Kaplan-Meier method, and compared between arms using the log-rank and Wilcoxon tests. The incidence of grade 3 and 4 toxicity was compared using Pearson's chi-squared test. Results: From Jan 2000 to Jan 2003, 206/354 patients were randomized, 138 on arm A and 68 on arm B. There were 98/40 males/females on arm A and 53/15 on arm B, while 36/102 on arm A and 16/52 on arm B had stage IIIB/IV disease (p=0.7). The median age for arm A and B, respectively, was 58 (range, 30–77) and 56 years (range, 38–74) (p=0.3). A KPS of ≥80/<80 was reported in 113/25 patients on arm A vs 57/11 patients on arm B (p=0.8). Preliminary data indicate a significant benefit in terms of TTPD for patients treated with gemcitabine maintenance therapy: 6.6 vs 5.0 months (through the study; p<0.001) and 3.5 vs 2.0 months (post randomization; p<0.001). Conclusions: At the present time of analysis, maintenance chemotherapy with gemcitabine following GC chemotherapy significantly increased TTPD. Final data will be presented at the meeting. No significant financial relationships to disclose.

Adjuvant gemcitabine and cisplatin (GC) for locally advanced cancer of the bladder after radical cystectomy: A USC experience with molecular correlates

4639 Background: Invasive bladder cancer has a 50% mortality rate. Adjuvant chemotherapy is used to try to improve survival, but is of unproven benefit. GC and MVAC have similar response rates and survival in the metastatic setting, with GC having less toxicity (JCO 17: 3068). We have used the GC regimen for patients with high grade bladder cancer with poor prognostic features after cystectomy when they have not been candidates for MVAC for medical or personal patient reasons. Methods: We conducted a retrospective study of patients treated with adjuvant chemotherapy between 1997 and 2002. Chemotherapy consisted of 3–4 cycles of adjuvant Gemcitabine 1000mg/m2 (days 1 & 8) and Cisplatin (35mg/m2 days 1 & 2). All patients undergoing radical cystectomy and receiving adjuvant GC at USC were eligible. Medical records were examined and tissues were studied for various molecular markers, including p53, ribonucleotide reductase (RR) and ERCC1. Results: 25 patients met inclusion criteria. Median age was 68; 72% were pT3 or pT4; 68% had lymph nodes involved. All patients had transitional cell carcinoma. P53 was mutated in 75%. The median number of cycles of GC was 3 (84% had 3–4 cycles). 11 patients (44%) had grade 3 or 4 hematologic toxicity and 2 (8%) had grade 3 non-hematologic toxicity. Median follow-up was 25.1 (8.7–49.7) months. 8 patients have died. The median time to recurrence was 49.7 (12.3–49.7+) months with median overall survival of 49.7+ (16.6–49.7+) months. Evaluation of tissue blocks for molecular correlates such as ERCC1 and RR is in progress and will be reported. Conclusions: Adjuvant GC chemotherapy is feasible and effective in the setting of locally advanced bladder carcinoma and will be studied in a prospective, randomized fashion. For the 17 patients with node-positive bladder cancer, adjuvant GC is associated with disease-free median survival of 23.6 (11.3, 49.7+) months and median survival of 23.8+ (16.6, 49.7+) months. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly

Combination of gemcitabine and cisplatin (GC) chemotherapy for advanced or recurrent nasopharyngeal cancer (NPC): A phase II study

5577 Background : Combination of GC chemotherapy is active and has a favorable safety profile in some several solid tumors, including advanced squamous cell head and neck cancers. We evaluated the efficacy and toxicity of this combination in advanced or recurrent NPC. Methods : In a two-center phase II study, patients with histologically confirmed advanced or recurrent NPC, measurable disease, WHO PS 0–2, age 19–70 years, adequate organ function, and written informed consent, were treated with Gemcitabine 1250 mg/m2 day 1 and day 8; Cisplatin 80 mg/m2 day 1 every 3 weeks. Primary endpoint was objective response rate. Results : Thirty five patients were enrolled between 12/01 and 11/03. There were 27 male and 8 female, 33 with Javanese ethnicity and 2 Caucasian;. with a mean age was 45 years (19–68). All but 3 patients (91.4%) had undifferentiated histology. Twenty-two patients had metastatic or recurrent disease, 13 patients had locally advanced disease. All patients were chemonaive, and 10 patients had recurrent disease after radiotherapy. There were 2 complete responses and 22 partial responses, yielding an 83% overall response rate from in 29 evaluable patients (95 CI, 68% - 97%). Grade 4 liver toxicity was found in 2 of 166 (1.2%) cycles analyzed. Grade III/IV anemia, neutropenia and thrombocytopenia were found in 1.8%, 8.2% and 1.2% of cycles respectively. Two patients are still on treatment. With a median follow-up of 9 months (1–21), the median progression-free survival and overall survival are 9 and 19 months, respectively. Conclusion : Gemcitabine and cisplatin combination is effective and has a safe toxicity profile for advanced and recurrent NPC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Elli Lily

Adjuvant gemcitabine and cisplatin (GC) for locally advanced cancer of the bladder after radical cystectomy: A USC experience with molecular correlates

4639 Background: Invasive bladder cancer has a 50% mortality rate. Adjuvant chemotherapy is used to try to improve survival, but is of unproven benefit. GC and MVAC have similar response rates and survival in the metastatic setting, with GC having less toxicity (JCO 17: 3068). We have used the GC regimen for patients with high grade bladder cancer with poor prognostic features after cystectomy when they have not been candidates for MVAC for medical or personal patient reasons. Methods: We conducted a retrospective study of patients treated with adjuvant chemotherapy between 1997 and 2002. Chemotherapy consisted of 3–4 cycles of adjuvant Gemcitabine 1000mg/m2 (days 1 & 8) and Cisplatin (35mg/m2 days 1 & 2). All patients undergoing radical cystectomy and receiving adjuvant GC at USC were eligible. Medical records were examined and tissues were studied for various molecular markers, including p53, ribonucleotide reductase (RR) and ERCC1. Results: 25 patients met inclusion criteria. Median age was 68; 72% were pT3 or pT4; 68% had lymph nodes involved. All patients had transitional cell carcinoma. P53 was mutated in 75%. The median number of cycles of GC was 3 (84% had 3–4 cycles). 11 patients (44%) had grade 3 or 4 hematologic toxicity and 2 (8%) had grade 3 non-hematologic toxicity. Median follow-up was 25.1 (8.7–49.7) months. 8 patients have died. The median time to recurrence was 49.7 (12.3–49.7+) months with median overall survival of 49.7+ (16.6–49.7+) months. Evaluation of tissue blocks for molecular correlates such as ERCC1 and RR is in progress and will be reported. Conclusions: Adjuvant GC chemotherapy is feasible and effective in the setting of locally advanced bladder carcinoma and will be studied in a prospective, randomized fashion. For the 17 patients with node-positive bladder cancer, adjuvant GC is associated with disease-free median survival of 23.6 (11.3, 49.7+) months and median survival of 23.8+ (16.6, 49.7+) months. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly