Palbociclib combined with endocrine treatment in hormone receptor-positive, HER2-negative breast cancer patients with high relapse risk after neoadjuvant chemotherapy: subgroup analyses of premenopausal patients in PENELOPE-B.

BACKGROUND: The PENELOPE-B study demonstrated that the addition of 1-year post-neoadjuvant palbociclib to endocrine therapy (ET) in patients with high-risk early breast cancer (BC) did not improve invasive disease-free survival (iDFS) compared to placebo. Here, we report results for premenopausal women. PATIENTS AND METHODS: Patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative BC at high risk of relapse [defined as no pathological complete response after neoadjuvant chemotherapy and a clinical, pathological stage, estrogen receptor, grading (CPS-EG) score ≥3 or 2/ypN+] were randomized to receive 13 cycles of palbociclib or placebo + standard ET. Ovarian function (OF) was evaluated by centrally assessed estradiol, follicle-stimulating hormone and anti-Müllerian hormone serum levels. RESULTS: Overall, 616 of 1250 randomized patients were premenopausal; of these, 30.0% were <40 years of age, 47.4% had four or more metastatic lymph nodes, and 58.2% had a CPS-EG score ≥3. 66.1% of patients were treated with tamoxifen alone, and 32.9% received ovarian function suppression (OFS) in addition to either tamoxifen or aromatase inhibitor (AI). After a median follow-up of 42.8 months (97.2% completeness) no difference in iDFS between palbociclib and placebo was observed [hazard ratio = 0.95, 95% confidence interval (CI) 0.69-1.30, P = 0.737]. The estimated 3-year iDFS rate was marginally higher in the palbociclib arm (80.6% versus 78.3%). Three year iDFS was higher in patients receiving AI than tamoxifen plus OFS or tamoxifen alone (86.0% versus 78.6% versus 78.0%). Patients receiving tamoxifen plus OFS showed a favorable iDFS with palbociclib (83.0% versus 74.1%, hazard ratio = 0.52, 95% CI 0.27-1.02, P = 0.057). Hematologic adverse events were more frequent with palbociclib (76.1% versus 1.9% grade 3-4, P < 0.001). Palbociclib seems not to negatively impact the OF throughout the treatment period. CONCLUSIONS: In premenopausal women, who received tamoxifen plus OFS as ET, the addition of palbociclib to ET results in a favorable iDFS. The safety profile seems favorable and in contrast to chemotherapy palbociclib does not impact OF throughout the treatment period.

Avances en el tratamiento del cáncer escamoso de cabeza y cuello / Development on squamous-cell cancer of the head and neck

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Biomarkers and anti-EGFR therapies for KRAS wild-type metastatic colorectal cancer

Therapy for metastatic colorectal cancer has been improved in terms of response rate, time to progression and overall survival by the emergence of anti-EGFR monoclonal antibodies (cetuximab and panitumumab) in combination with standard cytotoxic chemotherapy (oxaliplatin or CPT-11-based combinations). However, the benefits of cetuximab and panitumumab are confined to KRAS wild-type (KRAS-wt) colorectal tumours; KRAS-mutated tumours rarely respond to these drugs. Of all colorectal tumours, 65% are KRAS-wt tumours, but anti-EGFR therapies are effective for only 60-70% of these. Therefore, other biomarkers and molecular pathways must be involved in the response to anti-EGFR therapies in KRASwt colorectal tumours. Factors that may explain the lack of response include EGFR ligands, EGFR phosphorylation levels, the number of EGFR copies, the status of the KRAS effector B-RAF and the alternative intracellular PIK3CA/ PTEN/AKT and JAK/STAT signalling pathways. A battery of biomarkers is needed to select the patients that will be most sensitive to anti-EGFR therapies. Such patterns may be a novel and cost-effective tool to develop tailored treatments. This manuscript will review biomarkers and molecular pathways that are involved in the tumour response to anti-EGFR therapies (AU)

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Successful rectal cancer local recurrence radiofrequency ablation

Local rectal cancer recurrences represent a great challenge, as surgical re-excisions or re-irradiation procedures are not always feasible. Moreover, scar or local recurrence is hard to elucidate with conventional diagnosis techniques. Emerging diagnostic and therapeutic procedures may be useful in this setting. A local rectal cancer recurrence radiofrequency ablation is reported. PET scan confirmed the recurrence, defined the target volume and assessed the success of the local therapy (AU)

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Adjuvant chemotherapy for early-stage non-small-cell lung cancer. Single-centre experience and literature review

BACKGROUND: In recent years platinum-based chemotherapy has become the standard of care for patients with good performance status after complete resection in stages IB-IIIA non-small-cell lung cancer (NSCLC), although the benefit is mainly in stages II and IIIA. PATIENTS AND METHODS: In a retrospective trial we evaluate the clinical efficacy and toxicity profile of a platinum- and taxanes-based adjuvant chemotherapy in completely resected IB-IIIA NSCLC. The primary end point was relapse- free survival (RFS); principal secondary end points were overall survival (OS) and safety of the regimen. Potential predictive factors of efficacy and clinical patterns of relapse were also analysed. RESULTS: From January 2003 to December 2006, 41 patients met the inclusion criteria and were evaluable. Median age at diagnosis was 68.1 years (CI 95% 54-72; range 45-78). Most patients were males (87.7%) and had an Eastern Cooperative Oncology Group performance status score (PS) of 0-1 (87.8%), and 53.6% had adenocarcinomas. Pathological stages were as follow: 48.7% stage IB, 24.3% stage II and 26.8% stage IIIA. 75.6% of patients underwent a lobectomy and mediastinal lymphadenectomy and were treated with a combination of carboplatin AUC6 and paclitaxel 200 mg/m2 (85.36%) for 3 or 4 cycles. With a median follow-up of 18.2 months (range 5.1-46.5), 26 patients (63%) were free of disease and 32 of them were alive (78%). Median RFS was 12.1 months (CI 95% 9.8-14.9) and median OS had not been reached at the time of analysis. Patients with PS< or =1 at diagnosis had a higher RFS [p=0.051 (CI 95% 0.90-0.96)]. Toxicity was generally mild and haematologic events were the most frequent. Non-haematologic toxic effects of chemotherapy were asthenia/ anorexia (12.2%), nausea/vomiting (12.2%) and peripheral neuropathy (17%), but severe toxic effects (grade 3 or greater) were uncommon (<10%). We did not observe treatment-related deaths. CONCLUSIONS: Platinum-taxane-based adjuvant chemotherapy in IB-IIIA NSCLC following complete resection is feasible, well tolerated and can be delivered in most patients in the adjuvant setting. Ongoing molecular studies may have value in determining which patients will benefit from adjuvant chemotherapy (AU)

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Pathological complete response following docetaxel-based neoadjuvant chemotherapy for locally advanced gastric adenocarcinoma

Locally advanced gastric adenocarcinoma has a poor outcome. Neoadjuvant treatment is being tested in locally advanced non-resectable tumours and in those resectable tumours with a high risk of recurrence. Efforts to identify prognostic factors and more active and less toxic preoperative regimens are being searched for. We report the case of a patient achieving a complete histopathological complete response following docetaxel- based neoadjuvant chemotherapy (AU)

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Significance of the immunohistochemical detection of lymph node micrometastases in stage II colorectal carcinoma

BACKGROUND: Survival results of stage II colorectal cancer patients have led to major efforts to identify the subset of patients at risk for disease relapse and adjuvant therapies benefit. Immunohistochemistry is being explored to detect undetectable microscopic lymph node micrometastases. MATERIAL AND METHODS: A retrospective analysis of a 105 consecutive stage II colorectal cancer patients was performed. Two four-micres sections were obtained from each lymph node. These slides were stained with AE1-AE3 monoclonal antibodies against cytoskeleton using DAKO EnVision visualization system. Micrometastases were identified either as isolated cells or as well-defined glandular cell clusters with cytoplasm but not the nucleus stained with cytoskeleton antibodies. RESULTS: 665 lymph nodes isolated from 105 patients were analyzed. Lymph nodes micrometastases were assessed in 26 out of the 105 patients. 42 (6.3%) out of 665 lymph nodes were infiltrated. Most of these metastases consisted of isolated cell cluster localized in marginal and interfollicular sinus of lymph nodes. The relapse rate was 23.1% among the patients with immunohistochemical detected lymph node micrometastes and 20.3% for the patients without lymph node involvement. This result lacked statistical significance (p = 0.759). DISCUSSION: AE1/AE3 lymph node immunohistochemical staining in stage II colorectal cancer is an interesting biological phenomenon but it fails to identify patients at higher risk of relapse who deserve a more aggressive adjuvant attitude (AU)

Circulating tumoral cells lack circadian-rhythm in hospitalized metastasic breast cancer patients

BACKGROUND: The relationship between breast cancer and circadian rhythm variation has been extensively studied. Increased breast tumorigenesis has been reported in melatonin-suppressed experimental models and in observational studies. OBJECTIVES: Circulating Tumor Cells (CTC) circadian- rhythm may optimize the timing of therapies. This is a prospective experimental study to ascertain the day-time and night-time CTC levels in hospitalized metastasic breast cancer (MBC) patients. MATERIAL AND METHODS: TC are isolated and enumerated from a 08:00 AM and 08:00 PM blood collections. 23 MBC and 23 healthy volunteers entered the study. 69 samples were collected (23 samples at 08:00 AM and 23 samples at 08:00 PM from MBC; 23 samples from healthy volunteers). Results from two patients were rejected due to sample processing errors. No CTC were isolated from healthy-volunteers. RESULTS AND DISCUSSION: No-differences between daytime and night-time CTC were observed. Therefore, we could not ascertain CTC circadian-rhythm in hospitalized metastasic breast cancer patients (AU)

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)