The objective of this phase II trial was to assess the efficacy and toxicity of weekly paclitaxel for patients with metastatic or unresectable angiosarcoma.
Thirty patients were entered onto the ...study from April 2005 through October 2006. Paclitaxel was administered intravenously as a 60-minute infusion at a dose of 80 mg/m(2) on days 1, 8, and 15 of a 4-week cycle. The primary end point was the nonprogression rate after two cycles.
The progression-free survival rates after 2 and 4 months were 74% and 45%, respectively. With a median follow-up of 8 months, the median time to progression was 4 months and the median overall survival was 8 months. The progression-free survival rate was similar in patients pretreated with chemotherapy and in chemotherapy-naïve patients (77% v 71%). Three patients with locally advanced breast angiosarcoma presented partial response, which enabled a secondary curative-intent surgery with complete histologic response in two cases. One toxic death occurred as a result of a thrombocytopenia episode. Six patients presented with grade 3 toxicities and one patient presented with a grade 4 toxicity. Anemia and fatigue were the most frequently reported toxicities.
Weekly paclitaxel at the dose schedule used in the current study was well tolerated and demonstrated clinical benefit.
Ibrutinib plus venetoclax, given with an ibrutinib lead-in, has shown encouraging clinical activity in early phase studies in mantle cell lymphoma (MCL). The ongoing phase 3 SYMPATICO study evaluates ...the safety and efficacy of concurrently administered, once-daily, all-oral ibrutinib plus venetoclax in patients with relapsed/refractory MCL. A safety run-in (SRI) cohort was conducted to inform whether an ibrutinib lead-in should be implemented for the randomized portion. Patients received concurrent ibrutinib 560 mg continuously plus venetoclax in a 5-week ramp-up to venetoclax 400 mg for up to 2 years. The primary endpoint was occurrence of tumor lysis syndrome (TLS) and dose-limiting toxicities (DLTs). The SRI cohort enrolled 21 patients; six and 15 were in low- or increased-risk categories for TLS, respectively. During the 5-week venetoclax ramp-up, three patients had DLTs, and one patient at increased risk for TLS had a laboratory TLS; no additional TLS events occurred during follow-up. With a median follow-up of 31 months, the overall response rate was 81% (17/21); 62% (13/21) of patients had a complete response. SRI data informed that the randomized portion should proceed with concurrent ibrutinib plus venetoclax, with no ibrutinib lead-in. Ibrutinib plus venetoclax demonstrated promising efficacy; no new safety signals were observed. Trial registration: ClinicalTrials.gov, NCT03112174. Registered 13 April 2017, Keywords: Hematological cancers/lymphomas, Small molecule agents/kinase inhibitors, Ibrutinib, Venetoclax, Safety
In 2011 we reported a rituximab plus miniCHOP (reduced-dose cyclophosphamide, doxorubicin, vincristine, and prednisone) combination for patients older than 80 years with diffuse large B-cell lymphoma ...(DLBCL). The 2-year overall survival was 59% (95% CI 49-67) with an excess of early toxicity. To improve those results we tested the same chemotherapy protocol in combination with ofatumumab and a pre-phase treatment.
For this open-label, multicentre, single-group, phase 2 trial, we recruited patients older than 80 years with untreated histologically-proven CD20-positive DLBCL, Ann Arbor stage I to IV, from 41 academic and hospital centres in France and Belgium. Patients received a pre-phase with oral vincristine (1 mg total dose 1 week before cycle 1 day -7) and oral prednisone (60 mg total dose starting 1 week before cycle 1, for 4 days day -7 to day -4) before the first cycle of the ofatumumab plus miniCHOP regimen. The regimen consisted of 1000 mg total dose of intravenous ofatumumab, 25 mg/m
of intravenous doxorubicin, 400 mg/m
of intravenous cyclophosphamide, and 1 mg of intravenous vincristine, on day 1 of each cycle; and 40 mg/m
of oral prednisone on days 1-5. Ofatumumab was administered with 1000 mg of paracetamol and 50 mg of diphenhydramine. The primary endpoint was overall survival in the intention-to-treat population. The statistical analysis has been done on an intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT01195714.
Between June 2, 2010, and Nov 4, 2011, we enrolled 120 patients. Age-adjusted International Prognostic Index was 2-3 in 68 (57%) of them. The median follow-up time was 26·8 months (IQR 24·5-30·1). The 2-year overall survival was 64·7% (95% CI 55·3-72·7) and median overall survival was not reached (95% CI 30·2-not reached). 45 patients died during the treatment, of whom 28 (62%) died due to lymphoma. The most common side-effect was haematological toxicity. Among the 120 patients, grade 3-4 neutropenia was reported in 24 (21%) patients and thrombocytopenia in two (2%), during the treatment period. Grade 3-4 anaemia was reported in six (5%) patients; seven (6%) patients had one episode of febrile neutropenia. 17 (15%) of 115 patients in the modified intention-to-treat population had red blood cell transfusions and three (3%) had platelet transfusions.
Our result suggest that, in patients older than 80 years with DLBCL, ofatumumab and pre-phase treatment seem to improve overall survival compared with the previously reported data. The combination of pre-phase treatment, a monoclonal antibody against CD20, and miniCHOP can be considered a new treatment platform for use in randomised clinical trial design for DLBCL treatment in patients older than 80 years.
The Lymphoma Study Association, GlaxoSmithKline.
The combination of carmustine, etoposide, cytarabine, and melphalan (BEAM) as conditioning regimen prior to autologous stem-cell transplantation (ASCT) remains the standard of care for patients with ...mantle cell lymphoma (MCL) who are eligible for transplantation. The replacement of carmustine with bendamustine (BeEAM) was described as a promising alternative in non-Hodgkin lymphoma. The aim of this retrospective study was to compare the BeEAM with the BEAM regimen in MCL patients in the frontline setting. Sixty and 108 patients were included in the BeEAM and the BEAM groups, respectively. At 3 years, progression-free survival (PFS) was significantly higher in the BeEAM than in the BEAM group (84% 73-96 vs. 63% 51-79, p = 0.03). The overall survival was not statistically different between the two groups (p = 0.2). In multivariable analysis, BeEAM regimen remained associated with higher PFS (HR = 0.377, 95% CI, 0.146-0.970; p = 0.043). Subgroup analyses in patients treated with prior rituximab-aracytine induction alone showed that BeEAM improved the PFS compared with BEAM regimen (p = 0.04). Despite the high rate of acute renal failure KDIGO III (32%), treatment-related mortality was not increased with the BeEAM regimen. A prospective randomized trial will be necessary to confirm the beneficial effect of the BeEAM regimen in MCL patients undergoing ASCT.
Background
Providing cancer patients with adequate information is essential to their confidence and satisfaction regarding medical care. The aims of this study were to evaluate the information given ...to patients undergoing total pharyngolaryngectomy (TPL) as well as the evolution and predictors of patient quality of life (QoL).
Methods
We conducted a prospective multicentric study on patients undergoing TPL for a locally advanced laryngeal/hypopharyngeal cancer. All patients completed the EORTC QLQ-INFO25, QLQ-C30, and QLQ-H&N35 questionnaires, before and after surgery.
Results
This study enrolled 46 patients. Between the pre- and post-therapeutic periods, we observed no significant changes in the global QLQ-INFO25 and QLQ-C30 scores. However, we found a significant deterioration in 4 QLQ-INFO25 scales/items and in social functioning, as well as an increase of sense, speech, and social contact problems. N-stage and professional activity were significant predictors of preoperative QLQ-INFO25 scores. Younger age was significantly associated with financial difficulties, whereas professional activity and lower education level were significant predictors of xerostomia and swallowing problems, respectively.
Conclusion
In patients undergoing TPL, we observed significant changes in QLQ-INFO25 scores between the pre- and post-treatment periods and, particularly, a deterioration of patient satisfaction with the information received. Several clinical factors were identified as significant predictors of QLQ-INFO25 and QoL scores.
To evaluate the clinical outcomes of total pharyngolaryngectomy (TPL) in the elderly and to analyze the impact of age on postoperative complications and oncologic and functional outcomes.
We ...conducted a retrospective review of the medical records of all patients who underwent TPL for a laryngeal or hypopharyngeal squamous cell carcinoma, between 2000 and 2015. The impact of advanced age (>70 years) on clinical outcomes was assessed in univariate and multivariate analyses.
A total of 245 patients (mean age = 66.4 years) were enrolled in this study including 91 (37%) patients aged over 70 years. In patients aged over 70 years, local and general complication rates were 36% and 10%, respectively. Five-year overall, cause-specific and recurrence-free survival rates were 36%, 52% and 31%, respectively. Satisfactory swallowing (swallowing score ≥ 1; i.e. no enteral feeding) and speech (speech score ≥ 1; i.e. intelligible speech) functions were recovered by 94% and 70% of elderly patients. In multivariate analysis, older age had no significant impact on postoperative complications, oncologic outcomes and swallowing function. Compared to younger patients, elderly patients achieved significantly lower speech scores (p = 0.05).
TPL is associated with favorable clinical outcomes in patients aged over 70 years and can therefore be considered a reliable therapeutic option. However, compared to younger patients, a lower level of recovery regarding speech function is expected in the elderly, and particular attention should be paid to the postoperative speech rehabilitation program in this population of patients.
•Total pharyngolaryngectomy is associated with favorable clinical outcomes in the elderly.•Older age has no significant impact on postoperative complications.•Older age has no significant impact on oncologic outcomes and swallowing function.•Older age was associated with poorer recovery regarding speech function.
A higher risk of death from coronavirus disease 19 has been shown for patients with solid cancers or haematological malignancies (HM). Thanks to the accelerated development of anti–SARS-SoV-2 ...vaccines in less than a year since the start of the global pandemic, patients with cancer were quickly prioritised in early 2021 for vaccination, however dependent on the very unequal availability at the global level. Impaired immunogenicity of SARS-CoV-2 mRNA vaccines in immunocompromised patients was rapidly reported as early as April 2021, although the vaccination fortunately appears to be generally effective without increasing the spacing. Worryingly, the humoral response of the SARS-CoV-2 vaccination is, however, considered insufficient in patients followed for HM, in particular when they are on anti-CD20 treatment.
Thus, improving vaccination coverage by strengthening immune stimulation should be evaluated in patients under active treatment against cancer. Here, we discuss three different approaches: a third dose of early vaccine (repeated immune stimulation), heterologous prime-boost vaccination (multimodal immune stimulation) and a double-dose strategy (maximisation of immune response). Dedicated therapeutic trials, currently almost non-existent, seem rapidly necessary.
•Risks of hospitalisation and death increase for patients with cancer and coronavirus disease 19.•Patients with cancer should be prioritised for anti–SARS-CoV-2 vaccination.•Humoral response of SARS-CoV-2 mRNA vaccines is impaired in this population.•Ways of improving vaccination coverage for dedicated therapeutic trials are discussed.
BACKGROUND
Prognosis of recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) remains poor. The addition of cetuximab, to platinum and fluorouracil chemotherapy (EXTREME ...regimen) has been shown to improve patients’ outcomes in first‐line settings.
METHODS
We conducted a retrospective, multicenter study, including HNSCC that progressed after a first line of platinum‐based chemotherapy and cetuximab, treated either by paclitaxel + cetuximab (PC) or paclitaxel alone (P), between January 2010 and April 2018. The end points were overall survival (OS), progression‐free survival (PFS), and overall response rates (ORR). Patients were matched according to their propensity scores, estimated with a logistic regression model. The secondary objectives were to study the safety profile and to look for prognostic and predictive factors of effectiveness.
RESULTS
Of the 340 identified patients, 262 were included in the analysis, 165 received PC, and 97 received P. In unmatched population, ORR was 16.4% with PC and 6.2% for P. Median PFS was 2.9 months 95% Confidence Interval 2.7–3.0 for PC versus 2.5 months 2.2–2.7 for P, hazard ratio (HR) = 0.770 0.596–0.996. Median OS was 5.5 months 4.4–6.9 for PC versus 4.2 months 3.4–4.8 for P, HR = 0.774 0.590–1.015. In multivariate analysis, PC was associated with better PFS and OS. These results were consistent in matched‐paired population. Previous cetuximab maintenance for more than 3 months was predictive of better OS with PC.
CONCLUSION
Although the continuation of cetuximab in combination with paclitaxel after EXTREME provides moderate benefit, it could be an interesting option for selected patients.
In this propensity score‐adjusted, multi‐institutional series, cetuximab in association with paclitaxel showed better outcomes than paclitaxel alone for patients who had disease progression after EXTREME regimen, particularly for patients who benefit the most from cetuximab in first‐line setting. This study should raise the question of the place of this association with the arrival of immune checkpoint inhibitors in first line with or without chemotherapy.
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