Relative Dose Intensity Of Gemcitabine Research Articles

Safety and Efficacy of Gemcitabine Plus Cisplatin Against Recurrent/Metastatic Nasopharyngeal Carcinoma: A Retrospective Study.

Although gemcitabine plus cisplatin (GC) prolongs survival in patients with recurrent or metastatic nasopharyngeal carcinoma (R/M NPC) compared with fluorouracil plus cisplatin, no study has evaluated the efficacy and safety of GC in nonendemic regions, including Japan, yet. Therefore, we assessed the safety and efficacy of GC in Japanese patients with R/M NPC. We retrospectively reviewed patients with R/M NPC who received GC treatment at the Aichi Cancer Center Hospital from January 2017 to March 2020. The main eligibility criteria were histologically confirmed NPC, Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2, and locally recurrent disease unsuitable for local treatment or metastatic disease. The regimen was administered every 3 weeks (gemcitabine, 1,000 mg/m2 on days 1 and 8; cisplatin, 80 mg/m2 on day 1). Fourteen patients (median age, 58 years) were included in the study. Two patients had an ECOG PS of 2 and 11 exhibited nonkeratinizing histology. Of the eight patients with measurable lesions, one exhibited complete response and seven exhibited partial response, with an objective response rate of 75%. Median progression-free survival and overall survival were 7.7 and 24.2 months, respectively. Common grade 3 or 4 adverse events included neutropenia (64%), thrombocytopenia (14%), and febrile neutropenia (14%). The median relative dose intensity of gemcitabine and cisplatin was 62% and 60%, respectively. No treatment-related deaths occurred. The GC regimen demonstrates promising activity and is tolerable in Japanese patients with R/M NPC.

The impact of body composition on short-term outcomes of neoadjuvant chemotherapy with gemcitabine plus S-1 in patients with resectable pancreatic cancer.

Although the efficacy of neoadjuvant chemotherapy with gemcitabine plus S-1 (NAC GS) has recently been reported in resectable pancreatic cancer, severe adverse events were frequently observed. Sarcopenia has been reported to be associated with reduced antitumor response and chemotherapy toxicity in several malignancies. The aim of this study is to evaluate the impact of body composition on short-term outcomes of NAC GS in resectable pancreatic cancer patients. Clinicopathological data of consecutive patients treated with NAC GS at our institution from February 2019 to April 2020 were retrospectively reviewed. Anthropometric variables were calculated at the third lumbar vertebra using pretreatment computed tomography images. We investigated the association between body composition variables, and antitumor response and chemotherapy toxicity. Among 62 patients included in this study, 25 patients (40%) were sarcopenic at diagnosis. Sixty-one patients received surgery at our institution and 57 patients received pancreatic resection (R0/R1 resection 56/1). Fifty-six patients completed two cycles of NAC GS and severe adverse events (≥grade 3) occurred in 42 patients (hematologic toxicity 41 patients [66%]; non-hematologic toxicity 3 patients). Body mass index and total adipose tissue index were significantly lower in sarcopenic patients compared to non-sarcopenic patients. Completion rate of NAC, rate of treatment delay/interruption, relative dose intensity of gemcitabine and S-1, radiological and pathological tumor response after NAC were not different between sarcopenic and non-sarcopenic patients. Furthermore, there was no significant association between body composition, and severe adverse events and intolerance. In our experience, NAC GS was similarly tolerable and effective in resectable pancreatic cancer patients regardless of the presence of sarcopenia.

Postoperative Adjuvant Therapy for Resectable Pancreatic Cancer With Gemcitabine and Adoptive Immunotherapy

ObjectivesWe previously described adoptive immunotherapy (AIT) with cytotoxic T lymphocytes (CTLs) stimulated by the mucin 1 (MUC1)–expressing human pancreatic cancer cell line YPK-1 (MUC1-CTLs) and demonstrated that MUC1-CTLs might prevent liver metastasis. In the present study, we combined gemcitabine (GEM) and AIT for the treatment of pancreatic cancer.MethodsA total of 43 patients who underwent radical pancreatectomy received treatment with MUC1-CTLs and GEM. After surgery, MUC1-CTLs were induced and administered intravenously 3 times, and GEM administered according to the standard regimen for 6 months. The patients whose relative dose intensity of GEM was 50% or more and who received 2 or more MUC1-CTL treatments were used as the adequate treatment group (n = 21).ResultsIn the adequate treatment group, disease-free survival was 15.8 months, and overall survival was 24.7 months. Liver metastasis was found only in 7 patients (33%), and local recurrence occurred in 4 patients (19%). The independent prognostic factor of long-term disease-free survival on multivariate analysis was the average number of CTLs administered (P = 0.0133).ConclusionsThe combination therapy with AIT and GEM prevented liver metastasis and local recurrence. Moreover, the disease free-survival was improved in patients who received sufficient CTLs.

Gemcitabine monotherapy in patients with heavily treated nasopharyngeal cancer: a case series.

Although gemcitabine is thought to play a critical role in the treatment of nasopharyngeal cancer, no research to evaluate the efficacy and toxicity of gemcitabine monotherapy has been conducted in Japan. We retrospectively reviewed eight nasopharyngeal carcinoma patients treated with gemcitabine monotherapy at National Cancer Center Hospital East between May 2015 and August 2016. The main eligibility criteria were (1) histopathologically proven NPC; (2) tumor recurrence or an initial M1 TNM stage diagnosis; (3) at least two other types of systemic chemotherapy prior to gemcitabine; (4) no other active malignant tumor during treatment. All patients were administered gemcitabine 800-1000mg/m2 on days 1, 8, and 15, repeated every 4weeks. Gemcitabine was given as third-line systemic chemotherapy in six (74%) patients, as fourth-line in one (13%) and as fifth-line in one (13%). One patient had a complete response and one had a partial response, giving an overall response rate of 25%; four patients (50%) had stable disease and two (25%) experienced disease progression. The main toxicity was myelosuppression, with grade 3 leukopenia in three (38%) patients and neutropenia in four (50%). There were no treatment-related deaths. Median dose intensity and relative dose intensity of gemcitabine were 620mg/m2/week and 97.5%, respectively. Our findings suggest that GEM monotherapy is well tolerated and has potential as an active agent in Japanese patients with recurrent/metastatic NPC who have been heavily pretreated.

The relationship between antitumor effects and relative dose intensity of gemcitabine plus nab-paclitaxel for unresectable pancreatic cancer.

419 Background: Gemcitabine plus nab-paclitaxel (GEM+nab-PTX) is the standard first-line chemotherapy for unresectable pancreatic cancer, but the relationship between antitumor effects and relative dose intensity (RDI) remains unclear. Methods: A retrospective analysis of pancreatic cancer patients treated with GEM+nab-PTX as first-line chemotherapy between January 2015 and July 2016 at Cancer Institute Hospital of JFCR was performed. The RDI of GEM+nab-PTX was calculated as the delivered dose intensity divided by standard dose intensity. The patients were divided into two groups by median RDI. Kaplan Meier curves were constructed in order to analyze progression-free survival (PFS), time to treatment failure (TTF) and overall survival (OS), and differences between the two groups were compared with a log-rank test. Results: A total of 102 patients (52 male, a median age of 66 years) were enrolled. Eighty-two (80%) had metastatic disease. The best overall response was partial response in 30 (29%) and stable disease in 53 (52%). The median PFS, TTF and OS of the total cohort was 188 days (95% confidence interval: CI, 162 to 224), 161 days (95% CI, 146 to 183) and 369 days (95% CI, 309 to 440) respectively. The median RDI were 77% (range 30-100). In the RDI < 77% (n = 50) and the RDI ≥ 77% (n = 52) groups, the median PFS was 196 and 183 days (p = 0.33), the median TTF was 162 and 160 days (p = 0.186) and the median OS were 410 and 312 days (p = 0.10), respectively. Twenty-nine (28%) were eventually administered GEM+nab-PTX biweekly. The median RDI of biweekly regimen was 63% (range 29-86). The TTF of biweekly regimen and original weekly regimen was 196 and 160 days (p = 0.004) respectively. Conclusions: RDI is not a significant predictor of antitumor effects, and an appropriate dose reduction and extension of dosing interval may be permitted in pancreatic cancer patients treated with GEM+nab-PTX.

Gemcitabine Plus Platinum Combination Chemotherapy for Elderly Patients with Advanced Non-small Cell Lung Cancer: A Retrospective Analysis

PurposeThis study aimed to analyze the efficacy and toxicity of gemcitabine plus platinum chemotherapy for patients aged 70 years or older with advanced non-small-cell lung cancer (NSCLC).Materials and MethodsWe reviewed the records of stage IIIB, IV NSCLC patients or surgically inoperable stage II, IIIA NSCLC patients who were aged 70 years or older when treated with gemcitabine (1,250 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC5) chemotherapy from 2001 to 2010 at Seoul St. Mary's Hospital, Uijeongbu St. Mary's Hospital and St. Vincent's Hospital. Gemcitabine was administered on days 1 and 8, and cisplatin or carboplatin was administered on day 1. Treatments were repeated every 3 weeks for a maximum of 4 cycles.ResultsThe median age of the 62 patients was 73.5 years (range, 70 to 84 years). Forty-one (66%) patients exhibited comorbidity. The mean number of treatment cycles was 3.9. The compared average relative dose intensity of gemcitabine plus platinum chemotherapy was 84.8%. The median progression-free survival and overall survival (OS) were 5.0 months and 9.4 months, respectively. Reduced Eastern Cooperative Oncology Group (ECOG) performance status (none vs. ≥1) and weight loss (<5% vs. ≥5%) after treatment were found to have a significant effect on OS (p=0.01).ConclusionGemcitabine plus platinum chemotherapy is an effective treatment option with an acceptable level of toxicity in patients aged 70 years or older with good performance status in advanced NSCLC.

Gemcitabine plus UFT combination chemotherapy as second- or third-line therapy in non-small cell lung cancer: a pilot study

Gemcitabine plus UFT combination chemotherapy are highly effective and less toxic in the first line setting in patients with non-small cell lung cancer (NSCLC). The purpose of the study is to confirm the feasibility of this regimen as second- or third-line therapy in NSCLC. Fifteen patients with performance status of 0-1 were enrolled. UFT (tegafur 250 mg/m(2)/day) was administered orally twice a day from days 1-14, and gemcitabine of 900 mg/m(2) was administered intravenously on days 8 and 15 every three weeks on an outpatient setting. The treatment was repeated for at least 3 cycles and continued unless the disease progressed. The response rate and the disease control rate were 6.7% and 66.7%, respectively. Grade 3-4 toxicities included neutropenia in one patient and elevation of transaminases in one patient. The mean relative dose intensity of gemcitabine and UFT were 0.93 and 0.97, respectively. High disease control rate and less toxicity suggested the potential of gemcitabine and UFT combination chemotherapy as second- or third-line therapy in NSCLC.

A multicentre phase II study of cisplatin and gemcitabine for malignant mesothelioma

Our previous phase II study of cisplatin and gemcitabine in malignant mesothelioma showed a 47.6% (95% CI 26.2–69.0%) response rate with symptom improvement in responding patients. Here we confirm these findings in a multicentre setting, and assess the effect of this treatment on quality of life and pulmonary function. Fifty-three patients with pleural malignant mesothelioma received cisplatin 100 mg m−2 i.v. day 1 and gemcitabine 1000 mg m−2 i.v. days 1, 8, and 15 of a 28 day cycle for a maximum of six cycles. Quality of life and pulmonary function were assessed at each cycle. The best response achieved in 52 assessable patients was: partial response, 17 (33%, 95% CI 20–46%); stable disease, 31 (60%); and progressive disease, four (8%). The median time to disease progression was 6.4 months, median survival from start of treatment 11.2 months, and median survival from diagnosis 17.3 months. Vital capacity and global quality of life remained stable in all patients and improved significantly in responding patients. Major toxicities were haematological, limiting the mean relative dose intensity of gemcitabine to 75%. This schedule of cisplatin and gemcitabine is active in malignant mesothelioma in a multicentre setting. Investigation of alternative scheduling is needed to decrease haematological toxicity and increase the relative dose intensity of gemcitabine whilst maintaining response rate and quality of life.British Journal of Cancer (2002) 87, 491–496. doi:10.1038/sj.bjc.6600505 www.bjcancer.com© 2002 Cancer Research UK

Gemcitabine in advanced adult soft-tissue sarcomas. A phase II study of the EORTC Soft Tissue and Bone Sarcoma Group

Gemcitabine (2′-deoxy-2′-difluorocytidine monohydrochloride) at a dose of 1250 mg/m2 was given as a 30-min intravenous (i.v.) infusion on days 1 and 8 in a 3-weekly schedule to 32 patients with advanced soft-tissue sarcoma (STS) failing first-line chemotherapy. One patient was ineligible due to a delay between the previous chemotherapy and the start of treatment. Of the eligible patients, median age was 53 years (range 23–73 years). The predominant histological subtype was leiomyosarcoma in 12 patients (38%). The median number of cycles was three (range 1–8 cycles) with a median total dose of gemcitabine of 6.25 g/m2 (range 1.25–19.97 g/m2). The relative dose intensity of gemcitabine was 96% (range 50–103%). Treatment was tolerated very well with non-complicated haematological toxicity as the most frequently observed side-effect. Only one partial tumour response was documented, giving a response rate of 3.23% (95% Confidence Interval (CI): 0.08–16.2%). The median overall survival was 268 days (95% CI: 129–377) and the median time to progression was 45 days (95% CI: 41–79). These results indicate that gemcitabine given at this dose and schedule is not active as second-line therapy in advanced STS.

Docetaxel and Gemcitabine in Anthracycline-Resistant Advanced Breast Cancer: A Hellenic Cooperative Oncology Group Phase II Study

A phase II study was conducted to evaluate the activity and toxicity profile of the combination of docetaxel and gemcitabine in anthracycline-resistant advanced breast cancer (ABC). Thirty-nine eligible patients with a median performance status of I (range, 0–2) were enrolled in the study. Treatment consisted of docetaxel 75 mg/m2 in a 1-hr infusion on day 1 preceded by gemcitabine 1000 mg/m2 over 30 min on days 1 and 8. One hundred eighty-one treatment cycles were administered, 113 (62.4%) of them at full dose. Relative dose intensity of gemcitabine and of docetaxel was 0.73 and 0.85, respectively. More common grade 3–4 toxicities included neutropenia (49%), anemia (10%), fatigue (10%), nausea/vomiting (8%), and alopecia (77%). Seven patients were hospitalized for febrile neutropenia. Granulocyte colony-stimulating factor (G-CSF) administration was required in 90% of patients. Overall, 14 patients (36%) responded, 3 (7.5%) of them completely. Median duration of response was 10.3 months (range, 4.6–17.5+). Median time to progression was 7 months (range, 0.2–17.5+) and median survival 12.7 months (range, 2-–20.5+). In conclusion, the combination of docetaxel and gemcitabine, as used in the present study, has moderate activity in anthracycline-resistant ABC. Future studies should incorporate prophylactic administration of G-CSF to reduce the incidence of febrile neutropenia and maintain dose intensity.