Clinical outcomes of FOLFIRINOX and gemcitabine–nab paclitaxel for metastatic pancreatic cancer in the real world setting

Background/objectives The incidence of pancreatic cancer is increasing in developed countries. The incorporation of new therapies, to the first-line treatment of patients with good performance status led to better survival in clinical trials. However, there is a wide variability in their use and some concerns about the treatment of elderly patients who were not included in the clinical trials. Methods This is a retrospective multicenter study. Data from consecutive patients diagnosed with metastatic pancreatic cancer (mPC) treated with FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GnP) were analysed to evaluate efficacy (overall survival—OS) and toxicity. Results A total of 119 patients were included. 49.6% were treated with FFX and 50.4% with GNP in first-line. The median OS was 12 months with no statistically significant differences between both regimens (12.7 m for FFX vs 10.2 m for GnP). Elevated Ca 19.9 levels and neutrophil–lymphocyte ratio (NLR) increased the risk of death. Patients who received both regimens in first/second line had a median OS longer than 15 months whichever the sequence. 32 patients (27%) were older than 70-y. 54% patients received a second-line treatment, 56% in the FFX group and 44% in the GnP group. The median OS for patients older than 70 was 9.5 m versus 12.3 m for patients younger than 70. Progression of the disease was the cause of death in 67.6% of the patients. Conclusions In our setting, the use of FFX and GnP for treating mPC is quite similar, but superiority could not be demonstrated for any of the schemes in the first line. OS was determined by basal levels of Ca 19.9 and NLR. Patients receiving both regimens in first/second line whichever the sequence, exhibited the best survival rates. In our series, elderly patients had poorer survival rates (AU)

Clinical outcomes of FOLFIRINOX and gemcitabine-nab paclitaxel for metastatic pancreatic cancer in the real world setting.

BACKGROUND/OBJECTIVES: The incidence of pancreatic cancer is increasing in developed countries. The incorporation of new therapies, to the first-line treatment of patients with good performance status led to better survival in clinical trials. However, there is a wide variability in their use and some concerns about the treatment of elderly patients who were not included in the clinical trials. METHODS: This is a retrospective multicenter study. Data from consecutive patients diagnosed with metastatic pancreatic cancer (mPC) treated with FOLFIRINOX (FFX) or gemcitabine plus nab-paclitaxel (GnP) were analysed to evaluate efficacy (overall survival-OS) and toxicity. RESULTS: A total of 119 patients were included. 49.6% were treated with FFX and 50.4% with GNP in first-line. The median OS was 12 months with no statistically significant differences between both regimens (12.7 m for FFX vs 10.2 m for GnP). Elevated Ca 19.9 levels and neutrophil-lymphocyte ratio (NLR) increased the risk of death. Patients who received both regimens in first/second line had a median OS longer than 15 months whichever the sequence. 32 patients (27%) were older than 70-y. 54% patients received a second-line treatment, 56% in the FFX group and 44% in the GnP group. The median OS for patients older than 70 was 9.5 m versus 12.3 m for patients younger than 70. Progression of the disease was the cause of death in 67.6% of the patients. CONCLUSIONS: In our setting, the use of FFX and GnP for treating mPC is quite similar, but superiority could not be demonstrated for any of the schemes in the first line. OS was determined by basal levels of Ca 19.9 and NLR. Patients receiving both regimens in first/second line whichever the sequence, exhibited the best survival rates. In our series, elderly patients had poorer survival rates.

Recommendations and expert opinion on the treatment of locally advanced rectal cancer in Spain.

In Spain 22,000 new cases of colorectal cancer are diagnosed each year, with 13,075 deaths resulting from this disease. Around 70% of colorectal cancers are localised in the colon and 30% in the rectum. A group of Spanish experts established recommendations on what would be the best strategy in the treatment of locally advanced rectal cancer (LARC). Adequate assessment of local tumour extension, including high-resolution magnetic resonance imaging and endorectal ultrasound, is essential for successful treatment. The three cornerstones in the treatment of LARC are surgery, radiotherapy and chemotherapy. Most patients will need a total mesorectal excision (TME). Preoperative chemo-radiotherapy (CRT) is preferred for the majority of patients with T3/T4 disease and/or regional node involvement, and adjuvant chemotherapy is recommended after a patient-sharing decision. Capecitabine, after showing a trend in improved downstaging in neoadjuvant stratum and the convenience of its oral administration, represents an alternative to 5-FU as perioperative treatment of LARC.

Recommendations and expert opinion on the treatment of locally advanced rectal cancer in Spain

In Spain 22,000 new cases of colorectal cancer are diagnosed each year, with 13,075 deaths resulting from this disease. Around 70% of colorectal cancers are localised in the colon and 30% in the rectum. A group of Spanish experts established recommendations on what would be the best strategy in the treatment of locally advanced rectal cancer (LARC). Adequate assessment of local tumour extension, including high-resolution magnetic resonance imaging and endorectal ultrasound, is essential for successful treatment. The three cornerstones in the treatment of LARC are surgery, radiotherapy and chemotherapy. Most patients will need a total mesorectal excision (TME). Preoperative chemo-radiotherapy (CRT) is preferred for the majority of patients with T3/T4 disease and/or regional node involvement, and adjuvant chemotherapy is recommended after a patient-sharing decision. Capecitabine, after showing a trend in improved downstaging in neoadjuvant stratum and the convenience of its oral administration, represents an alternative to 5-FU as perioperative treatment of LARC (AU)

Randomized study of weekly irinotecan plus high-dose 5-fluorouracil (FUIRI) versus biweekly irinotecan plus 5-fluorouracil/leucovorin (FOLFIRI) as first-line chemotherapy for patients with metastatic colorectal cancer: a Spanish Cooperative Group for the Treatment of Digestive Tumors Study.

BACKGROUND: Irinotecan plus infusional 5-fluorouracil/leucovorin (FOLFIRI) is accepted as a reference treatment for the first-line treatment of patients with metastatic colorectal cancer (MCRC). The aim of this study was to demonstrate that a regimen without leucovorin (LV) (FUIRI) is not inferior to the standard FOLFIRI (response rate). PATIENTS AND METHODS: Chemotherapy-naive patients with MCRC were randomized to receive either irinotecan (180 mg/m(2) on day 1) + 5-fluorouracil (5-FU) (400 mg/m(2) bolus and 600 mg/m(2) 22-h infusion) + LV (200 mg/m(2) on days 1-2) (FOLFIRI) every 2 weeks or irinotecan (80 mg/m(2)) + 5-FU (2.250 mg/m(2) 48-h infusion) (FUIRI) weekly. RESULTS: In all, 346 patients were included, 173 in each arm. In the intention-to-treat analysis, the response rates for FOLFIRI and FUIRI were 57% [95% confidence interval (CI) 49% to 64%] and 51% (95% CI 43% to 59%), respectively (P = 0.2809). No statistically significant differences were observed between FOLFIRI and FUIRI regarding median progression-free survival (8.3 versus 8.4 months; P = 0.4339) nor median overall survival (21.6 versus 19.2 months; log-rank test P = 0.2941). Grade 3/4 neutropenia was significantly more frequent on FOLFIRI arm (27% versus 9%), while the proportion of diarrhea was higher on FUIRI arm (21% versus 42%). CONCLUSION: FUIRI represents a valid alternative without LV to the FOLFIRI regimen as MCRC first-line treatment.

Tratamiento inmediato o tardío con imipenem en pacientes con cáncer y neutropenia por quimioterapia a dosis altas: Resultados de un estudio comparativo aleatorizado / Immediate vs. delayed imipenem treatment in cancer patients with profound neutropenia induced by high-dose chemotherapy: Results of a randomized study

Se realizó un estudio para comparar el uso profiláctico de imipenem cuando aparece neutropenia intensa (tratamiento inmediato) y el uso terapéutico de imipenem cuando se inicia una fiebre neutropénica (tratamiento tardío) en pacientes con cáncer tratados con quimioterapia a dosis altas. Participaron 65 pacientes que iban a recibir dos ciclos de quimioterapia con ciclofosfamida, etopósido y cisplatino (CEP) a dosis altas. Se distribuyó aleatoriamente a los pacientes en dos grupos para recibir imipenem al aparecer neutropenia (brazo tratado con imipenem inmediato, brazo con tratamiento profiláctico) o bien al inicio de una fiebre relacionada con la neutropenia (brazo tratado con imipenem tardío, brazo con tratamiento terapéutico). Cuando se llevó a cabo el segundo ciclo de quimioterapia CEP, se cruzaron los tratamientos con imipenem. De los 65 pacientes, 41 recibieron los dos ciclos previstos y 24 sólo el primer ciclo. En comparación con el brazo de imipenem tardío, el brazo tratado con imipenem inmediato se asoció a una menor incidencia de fiebre (86,3 por ciento frente al 100 por ciento, p=0,0142) y a menos infecciones por gramnegativos (4/51 [7,8 por ciento] frente a 14/55 [25,5 por ciento], OR=0.24, p=0.031). Hubo menos episodios de neumonía (2 por ciento frente a 12,7 por ciento), "shock" séptico (0 por ciento frente a 3,6 por ciento) y muertes debidas a infección (0 por ciento frente a 3,6 por ciento), aunque estas diferencias no llegaron a ser estadísticamente significativas. Con respecto al imipenem de administración tardía, por cada siete pacientes tratados con imipenem inmediato se evitó un episodio de fiebre relacionada con la neutropenia; por cada seis pacientes tratados con imipenem inmediato se evitó un caso de infección por gramnegativos; y por cada nueve pacientes tratados con imipenem inmediato se evitó un episodio de neumonía. No hubo diferencias en la incidencia de infecciones por grampositivos ni en la duración de la hospitalización entre los dos brazos de tratamiento. En conclusión, y comparado con el uso tardío convencional, el tratamiento con imipenem inmediato reduce la frecuencia de neutropenia febril y las infecciones por gramnegativos en los pacientes que reciben quimioterapia a dosis elevadas. (AU)

Immediate vs. delayed imipenem treatment in cancer patients with profound neutropenia induced by high-dose chemotherapy: results of a randomized study.

A study was carried out to compare the use of prophylactic imipenem administered at the onset of profound neutropenia (immediate) with therapeutic imipenem administered at the onset of neutropenic fever (delayed) in cancer patients treated with high-dose chemotherapy. A total of 65 patients who were scheduled to receive two cycles of high-dose cyclophosphamide, etoposide, cisplatin (CEP) chemotherapy were randomized to receive imipenem either at presentation of neutropenia (immediate imipenem arm, prophylactic arm) or at commencement of neutropenic fever (delayed imipenem arm, therapeutic arm). Treatment was crossed over when the second CEP chemotherapy cycle was received. Of the 65 patients, 41 received the two planned cycles and 24 received only the first. Compared with the delayed imipenem arm, the immediate imipenem arm was associated with lower fever incidence (86.3% vs. 100%, p=0.0142) and Gram-negative bacteria infection [4/51 (7.8%) vs. 14/55 (25.5%), OR=0.24, p =0.031]. There were fewer episodes of pneumonia (2% vs. 12.7%), septic shock (0% vs. 3.6%) and deaths from infection (0% vs. 3.6%), but these differences did not reach statistical significance. With regard to delayed imipenem, for every seven patients with immediate imipenem, one episode of febrile neutropenia was avoided; for every six patients administered immediate imipenem, one case of Gram-negative infection was avoided; and for every nine patients administered immediate imipenem, one episode of pneumonia was avoided. There were no differences in the incidence of Gram-positive infections nor in the length of hospitalization between the two treatment arms. In conclusion, compared to its conventional delayed use, immediate imipenem significantly reduces the frequency of febrile neutropenia and Gram-negative infections in patients with high-dose chemotherapy.