The preservation of fungal cultures by lyophilization

A method for the preservation of fungal strains is presented. The cultures are grown on Sabouraud glucose agar in glass ampoules and lyophilized without further processing. By this method the macroscopical morphology of the cultures is preserved, so that these can be used immediately without recultivation as reference cultures. All tested mould and yeast strains remained viable over the six months duration of the experiment, whereas the dermatophyte strains could only partially be recultivated.     

Enzymatic activity of Microsporum canis and Trichophyton mentagrophytes from breeding rabbits with and without skin lesions

Microsporum canis and Trichophyton mentagrophytes are zoophilic dermatophytes which can cause skin infections in animals and humans. The clinical expression of this infection strongly varies depending on host, fungal species as well as enzyme production. No comparative studies are available on the enzymatic activities of M. canis and T. mentagrophytes isolated from breeding rabbits. Thus, the aim of this work was to assess the capability of M. canis and T. mentagrophytes isolated from rabbits both with and without lesions in producing different enzymes. The relationship of dermatophyte enzymatic activities and presence/absence of skin lesions has also been investigated. A total of 260 isolates of T. mentagrophytes and 25 isolates of M. canis sampled both from healthy and lesioned skin of rabbits, as well as from air samples of positive farms were examined. The results showed that T. mentagrophytes and M. canis from rabbits produce different enzymes. However, only elastase and gelatinase were linked to the appearance of lesions in T. mentagrophytes infections, whereas lipase in those by M. canis.     

Two cases of tinea ciliaris with blepharitis due to Microsporum audouinii and Trichophyton verrucosum and review of the literature

Dermatophytes are rarely taken into account among the causes of blepharitis. In our report, we describe a 69‐year‐old man and a 40‐year‐old woman with chronic blepharitis for 10 years and 4 years respectively, in whom we examined the scales and pulled eyelashes on direct microscopy and isolated Microsporum audouinii and Trichophyton verrrucosum in the culture. We emphasise that dermatophytes may play a role in the etiopathogenesis of chronic blepharitis. In chronic, treatment resistance blepharitis fungal infections may be considered as possible cause.     

Determination of Biogenous Amines in Fungus-Cultures (Candida albicans,Trichophyton mentagrophytes,Trichophyton rubrum and Microsporum canis) by Thin-Layer Chromatography and Mass-Spectrometry*

Summary: The biogenous amines methylamine, dimethylamine, ethylamine, ethanol-amine, piperidine, β-phenylethylamine, serotonine, pyridoxamine, hordenine, ammonia, isoamylamine, spermine and spermidine were qualitatively detected, and dimethylamine, ethanolamine, piperidine, β-phenylethylamine, serotonine and pyridoxamine and hodenine were quantitatively determined using two-dimensional thin-layer chromatography in Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum canis and Candida albicans treated with DANS, according to Seiler and Wiechmann's method. However, no methylamine was detected in Microsporum canis and no ethylamine in Candida albicans. The presence of a certain amine was established on the strength of identity of reference values, of colour spots and knowledge of the chemical transformation undergone. For quantitative analysis, the spectro-fluorometric reading of the DANS amide extracted from the silica-gel was used. The amine content varied between 10^-8 and 10^-11 moles per gram of fungus-culture for each amine and fungus-culture investigated. For each amine, the quantitiy present lay within a range of a power of ten. Only serotonine in Candida albicans was a power of ten higher than the rest. Histamine could not be detected. To confirm these results, the presence of serotonine, ethanolamine and piperidine in Candida albicans and the absence of histamine were investigated by identifying the amines as their t-dimethylamino-naphthaline-5-sulphonyl derivatives using-mass-spec-troscopy. The results confirmed the thin-layer chromatography results. Again, no histamine was detected. Zusammenfassung: Die biogenen Amine Methylamin, Dimethylamin, Äthylamin, Äthanolamin, Properdin, β-Phenäthylamin, Serotonin, Pyridoxamin, Hordenin, Ammoniak, Isoamylamin, Spermin und Spermidin wurden qualitativ, Dimethylamin, Äthanolamin, Piperdin, β-Phenäthylamin, Serotonin, Pyridoxamin und Hordenin quantitativ mittels zweidimensionaler Dünnschichtchromatographie nach Umsetzung mit 1-Dimethylamino-naphthalin-5-sulfonyl nach der Methode Seiler und Wiechmann inin Trichophyton mentagrophytes, Trichophyton rubrum, Microsporum canis und Candida albicans – mit Ausnahme von Methylamin bei Microsporum canis und Äthylamin bei Candida albicans – nachgewiesen. Identität der Rf-Werte, Fluorescenzfarbe und der Weg der Aufbereitung lassen die Annahme des Vorkommens der ge-nannten Amine zu. Zur quantitativen Analyse wurde die spektro-fluorimetrische Messung der aus Kiesel-gel eluierten DANS-Amide verwandt. Der Amingehalt bewegte sich zwischen 10^-8 bis 10^-11 Mol pro 1 Gramm Pilzkultur je nach Amin und untersuchter Pilzkultur. Der jeweilige Amingehalt lag bei den vier Pilzkulturen innerhalb einer Zehner-potenz; lediglich Serotonin war bei Candida albicans um eine Zehnerpotens höher. Histamin konnte nicht nachgewiesen werden. Um diese Ergebnisse zu sichern wurde das Vorhandensein von Serotonin, Äthanol-amin und Piperidin in Candida albicans und das Fehlen von Histamin durch massen-spektrometrische Identifizierung in Form ihrer DANS-Derivate untersucht. Die dünnschichtchromatrographischen Ergebnisse konnten massenspektrometrisch be-stätigt werden. Audi hierbei war Histamin nicht nachzuweisen.     

The Effect of 9a-FIuoroprednisolone on the Pathogenicity of Microsporum canis and Trichophyton violaceum to Horses/Die Wirkung von 9a-Fluorprednisolon auf die Pathogenität von Microsporum canis und Trichophyton violaceum für Pferde

Summary: Horses were successfully infected with human isolates of Microsporum canis and Trichophyton violaceum. The lesions produced by both dermatophytes followed a similar course of development Annular lesions of ringworm, reminiscent of those observed in natural infections, were produced by M. canis , while those produced by T. violaceum had no specific pattern. The lesions produced by M. canis developed earlier and were slightly more severe than those produced by T. violaceum. Premedication of the horses with 9a-fluoroprednisolone increased the severity of the experimentally induced lesions. Skin sections showed that a larger number of hair follicles were parasitized by the dermatophytes with a severer degree of invasion in horses premedicated with 9a-fluoroprednisolone than those which had not received this steroid.
Zusammenfassung: Pferde wurden erfolgreich mit vom Menschen isolierten Referenzstämmen von Microsporum canis und Trichophyton violaceum infiziert. Die Läsionen, die durch beide Dermatophyten gesetzt wurden, entwickelten sich in ähnlicher Weise. Ringförmige Tinea-Läsionen wurden durch M. canis verursacht, die an solche bei natürlichen Infektionen erinnerten, während die durch T. violaceum verursachten kein besonderes Muster zeigten. Die durch M. canis bedingten Läsionen entwickelten sich früher und waren etwas schwerer als die von T. violaceum verursachten. Die Vorbehandlung der Pferde mit 9a-Fluorprednisolon erhöhte den Schweregrad der experimented gesetzten Infektherde. Hautschnitte zeigten, daß eine größere Zahl von Haarfollikeln in stärkerem Ausmaß von den Dermatophyten bei den 9a-Fluorprednisolon-behandelten Pferden im Vergleich zu den unbehandelten befallen war.     

Frequency,type and treatment of fungal pathogens in toenail onychomycosis in the central Alpine region of South Tyrol,northern Italy – a 10‐year retrospective study from 2004 to 2013

Onychomycosis is one of the most common dermatological diseases, primarily caused by dermatophytes, and sometimes, also by yeast and moulds. This study aims to clarify the frequency of isolated pathogens from mycotic toenails in the reference centre of the central Alpine mountain region of South Tyrol, northern Italy. Age and gender differences, types of pathogens and initial therapy used were also investigated. This is a retrospective study from 2004 to 2013 on the files of all patients with suspected onychomycosis in whom a cultural pathogen detection was performed. A total of 1565 patients were studied (943 women; 622 men), with a median age of 55 years. Fungal pathogens could be detected by culture in 49.5%. Significantly more pathogens could be grown in men (63.8%) than in women (39.9%, P < 0.0001). The most common pathogens grown were dermatophytes (53.3%), especially T. rubrum and T. interdigitale, followed by moulds (24.7%) and yeast (22%). Therapies prescribed were topical in 64.2% and systemic in 35.8% of the cases. Topical treatment was more frequent in older patients (P < 0.05). In northern Italy, dermatophytes are the most common causative agents for onychomycosis. Fungal pathogens were more commonly found in men than in women and topical treatment was more frequent in older patients.     

Isolation of dermatophytes and other keratinophilic fungi from surface sediments of the Shatt Al-Arab River and its creeks at Basrah, Iraq

Summary. Twenty-five sediment samples were taken from randomly selected sites in the Shatt Al-Arab River and its creeks and analysed for dermatophytes and related keratinophilic fungi. The results revealed that out of 25 samples only 13 (52%) yielded dermatophytes and related keratinophilic fungi. A total of nine species in four genera were isolated. The most frequent genera isolated in this study were Chrysosporium and its teleomorph Aphanoascus . The species most frequently found were Aphanoascus julvescens, A. durus, Chrysosporium crassitunicatum, Chr. keratinophilum and Chr. tropicum (each n =3). Microsporum was represented by two species, namely M. fulvum and M. gypseum. Trichophyton was represented by one species, T. verrucosum . The occurrence of these fungi illustrates that sediments may act as a reservoir for potentially pathogenic fungi for human and animals.
Zusammenfassung. Fünfundzwanzig Sedimentproben wurden von zufällig ausgewählten Orten im Shatt Al-Arab-Fluß und seinen Neben-flüssen gewonnen und auf Dermatophyten und sonstige keratinophile Pilze untersucht. Es stellte sich heraus, daβ von 25 Proben nur 13 (52%) keratinophile Pilze enthielten. Insgesamt wurden neun Arten aus vier Gattungen isoliert. Die in dieser Studie am häufigsten isolierte Gattung war Chrysosporium und sein Teleomorph Aphanoascus . Die am häufigsten isolierten Arten waren Aphanoascus fulvescens, A. durus, Chrysosporium crassitunicatum, Chr. keratinophilum und Chr. tropicum. Microsporum war durch zwei Isolate repräsentiert, nämlich M. fulvum und M. gypseum. Trichophyton war nur durch die Art T. verrucosum vertreten. Flußsedimente können also als mögliches Reservoir für potentielle mensch- und tierpathogene Pilze angesehen werden.     

First-line therapy,autologous stem-cell transplantation,and post-transplantation maintenance in the management of newly diagnosed mantle cell lymphoma

BackgroundIn Ontario, no clearly defined standard of care for the management of mantle cell lymphoma (mcl) has been developed, and substantial variability from centre to centre is evident. This guidance document was prompted by the need to harmonize practice in Ontario with respect to first-line, conditioning, and post-transplantation maintenance therapy for patients newly diagnosed with transplantation-eligible mcl.MethodsThe medline and embase databases were systematically searched from January 2013 to January 2020 for evidence, and the best available evidence was used to draft recommendations relevant to first-line therapy, autologous stem-cell transplantation, and post-transplantation maintenance in the management of transplantation-eligible newly diagnosed mcl. Final approval of this guidance document was obtained from the Stem Cell Transplant Advisory Committee.RecommendationsThese recommendations apply to all cases of transplantation-eligible newly diagnosed mcl:

• ■ Alternating cycles of r-chop (rituximab plus cyclophosphamide–doxorubicin–vincristine–prednisolone) and r-dhap [rituximab plus dexamethasone–high-dose cytarabine–cisplatin] is the recommended first-line treatment for symptomatic patients newly diagnosed with mcl before autologous stem-cell transplantation (asct).
• ■ Rituximab plus hyperfractionated cyclophosphamide–vincristine–doxorubicin–dexamethasone (r–hypercvad), alternating with methotrexate and cytarabine, is not recommended for the treatment of patients with newly diagnosed mcl.
• ■ beam (carmustine–etoposide–cytarabine–melphalan), beac (carmustine–etoposide–cytarabine–cyclophosphamide), and total-body irradiation–based regimens are reasonable conditioning options for patients with mcl who have responded to first-line therapy and who are undergoing asct.
• ■ Maintenance therapy with rituximab is recommended for patients with newly diagnosed mcl who have undergone asct.

     

Isavuconazole treatment for rare fungal diseases and for invasive aspergillosis in patients with renal impairment: Challenges and lessons of the VITAL trial

Invasive fungal disease (IFD) confers a substantial risk for morbidity and mortality to immunocompromised patients. Invasive aspergillosis (IA) is the most common IFD caused by moulds but the prevalence of other rare mould diseases, such as mucormycosis, hyalohyphomycosis and phaeohyphomycosis, may be increasing. Treatments are available for IA, but evidence to support efficacy and safety of antifungal agents for rare IFDs, or for IFDs in special patient populations, is limited or lacking. The VITAL trial was conducted to assess the efficacy and safety of isavuconazole for the treatment of patients with IA and renal impairment, or with IFDs caused by rare moulds, yeasts or dimorphic fungi. These patients stand to benefit most from a new treatment option but are unlikely to be included in a randomised, controlled trial. In this article, we review the challenges faced in the design and conduct of the VITAL trial. We also review the findings of VITAL, which included evidence of the efficacy and safety of isavuconazole. Finally, we consider the importance of trials such as VITAL to inform therapeutic decision making for clinicians faced with the challenge of treating patients with rare IFDs and as one paradigm of how to determine efficacy and safety of new drugs for rare and resistant infections without a suitable comparator.     

Triplet combination of gemcitabine, paclitaxel, and carboplatin followed by maintenance 5-fluorouracil and folinic acid in patients with metastatic nasopharyngeal carcinoma

BACKGROUND.: Nasopharyngeal carcinoma (NPC) is a disease that is highly responsive to various chemotherapeutic agents. In the metastatic setting, 2-drug combination chemotherapy generally provides a response rate of 55% to 75%, and median survival of 10 to 12 months. The objective of the current study was to assess the efficacy of a 3-drug combination followed by maintenance treatment in patients with metastatic NPC. METHODS.: Patients with metastatic NPC were treated with a combination of gemcitabine at a dose of 1000 mg/m(2), paclitaxel at a dose of 70 mg/m(2), and carboplatin at an area under the concentration-time-curve (AUC) of 2.5 on Days 1 and 8 every 21 days. Patients who achieved partial or complete response continued to receive weekly 5-fluorouracil at a dose of 450 mg/m(2) and leucovorin at a dose of 30 mg/m(2) for 48 weeks. RESULTS.: Twenty-eight patients were recruited. Twenty-two (79%) patients had >/=2 sites of disease. Toxicities were mainly from bone marrow suppression, with 79% grade 3/4 neutropenia, 32% grade 3/4 anemia, and 29% grade 3/4 thrombocytopenia (according to the National Cancer Institute Common Toxicity Criteria). The overall response rate to the 3-drug regimen was 86%, with a complete response rate of 11%. The median duration of response was 8 months and the median overall survival was 22 months. CONCLUSIONS.: This regimen of a 3-drug combination followed by maintenance is feasible and has demonstrated an encouraging response rate and overall survival. Cancer 2008. (c) 2008 American Cancer Society.     

Long-term clinical and functional outcomes after treatment for localized Ewing's tumor of the lower extremity

PURPOSE: Retrospective review describing the 35-year University of Florida experience with Ewing's tumors of the lower extremity. PATIENTS AND METHODS: Fifty-three patients were treated between 1971 and 2006. Thirty patients were treated with radiotherapy (RT) alone and 23 patients were treated with surgery +/- RT. Larger tumors and tumors of the femur were treated more often with definitive RT. Median potential follow-up was 19.2 years. Functional outcome was assessed using the Toronto Extremity Salvage Score (TESS). RESULTS: Before 1985, 24% of patients were treated with surgery; since then, the rate has increased to 61%. The 15-year actuarial overall survival (OS), cause-specific survival (CSS), freedom from relapse, and limb preservation rates were 68% vs. 47% (p = 0.21), 73% vs. 47% (p = 0.13), 73% vs. 40% (p = 0.03), and 43% vs. 40% (p = 0.52), respectively, for patients treated with surgery +/- RT vs. RT alone. Excluding 8 patients who underwent amputation or rotationplasty, the 15-year actuarial local control rate was 100% for the surgery +/- RT group and 68% for the definitive RT group (p = 0.03). The ranges of the TESS for surgery +/- RT vs. RT alone were 70-100 (mean, 94) and 97-100 (mean, 99), respectively. Twenty-six percent (6/23) of patients had complications related to surgery requiring amputation or reoperation. CONCLUSIONS: Overall survival and CSS were not statistically compromised, but we observed an increased risk of relapse and local failure in patients treated with RT alone, thereby justifying a transition toward primary surgical management in suitable patients. However, despite an adverse risk profile, patients treated with RT alone had similar long-term amputation-free survival and demonstrated comparable functional outcomes. Poor results observed in Ewing's of the femur mandate innovative surgical and RT strategies.     

Antagonistic Reactions of the Moulds from Cattle-Feeds in Relation of Staphylococcus Aureus and Escherichia Coli, Pathogenic to Cattle

Summary: The antagonistic activity of 55 moulds isolated from various cattle feeds was determined by employing a filter paper diffusion technique. Four moulds, viz., Aspergillus chevalieri, two strains of Penicillium chrysogenum and Alternaria alternata showed wide zones of inhibition when tested against S. aureus hence considered strong antagonists but were weakly antagonistic with respect to E. coli. None of the moulds tested against E. coli was strongly antagonistic. Sixteen moulds showed a reaction of weak activity against both the pathogenic bacteria. Besides, four moulds which did not show any activity against E. coli, were weakly antagonistic to S. aureus and 11 moulds which were weakly antagonistic to E. coli were not so to S. aureus.
Zusammenfassung. Die antagonistische Aktivität von 55 Schimmelpilzen die aus Rinderfutter isoliert worden waren, wurde mit der Filterpapierdiffusionstechnik geprüft. 4 Schimmelpilze, nämlich Aspergillus chevalieri, 2 Stämme von Penicillium chrysogenum und Alternaria alternata zeigten große Hemmzonen bei Testung mit S. aureus und wurden daher als stark antagonistisch betrachtet während sie gegen E. coli nur schwach antagonistisch wirkten.
Keiner der getesteten Schimmelpilze zeigte starke Aktivität gegen E. coli. 16 Schimmelpilze zeigten eine schwache Aktivität gegen beide pathogenen Bakterien. 4 weitere Pilze besaßen keine Hemmwirkung auf E. coli, aber waren schwach wirksam gegen S. aureus. Schließlich waren 11 Schimmelpilze schwach antagonistisch gegen E. coli aber nicht gegen S. aureus.     

A randomized controlled trial to evaluate the role of interferon as initial and maintenance therapy in patients with follicular lymphoma.

The purpose of this study was to evaluate the role of interferon as initial and maintenance therapy in patients with newly diagnosed follicular lymphoma. Between 1984 and 1994, 204 patients with newly diagnosed Stage III or Stage IV follicular lymphoma were randomized to receive either, Chlorambucil (CB): 10 mg daily for 6 weeks, followed by a 2-week interval, with 3 subsequent 2-week treatment periods at the same dose, separated by 2-week intervals, or, CB given concurrently with interferon (IFN). IFN was given at a dose of 3 x 10(6)units thrice weekly, subcutaneously, throughout the 18-week treatment period. Responding patients were subsequently randomized to receive maintenance IFN at the dose and schedule described above, or to expectant management. The overall response rate was 161/204 (78%), complete remission being achieved in 24% of patients. Neither the addition of IFN to the initial treatment, nor the use of maintenance IFN influenced response rate, remission duration or survival. This study was undertaken to determine whether IFN, given in combination with, and then subsequent to, CB would alter the clinical course of patients with follicular lymphoma. Disappointingly, this objective was not achieved, no advantage having been demonstrated for the addition of IFN.     

奥布替尼维持治疗对老年或体弱中枢神经系统淋巴瘤患者的疗效和安全性分析

目的:探讨基于奥布替尼的维持治疗在老年或体弱中枢神经系统淋巴瘤(central nervous system lymphoma, CNSL)患者中的疗效及安全性。方法:回顾性分析2015年7月至2021年6月我院收治的18例CNSL患者,接受基于奥布替尼方案的维持治疗,观察其无进展生存期(PFS)和安全性。结果:在11例原发性中枢神经系统淋巴瘤(PCNSL)患者中,中位维持治疗5(IQR 2.3～8.5)个月后,6个月、12个月PFS率分别为63.6%、50.9%。在7例继发性中枢神经系统淋巴瘤(SCNSL)患者中,中位维持治疗7.7(IQR 5～9)个月后,6个月、12个月PFS率分别为100%、75%。在7例经诱导治疗达完全缓解的患者中,经过中位7.7(IQR 5～9.5)个月维持治疗后,6个月、12个月PFS率均为100%。有8例患者报告了3或4级不良反应。结论:基于奥布替尼方案的维持治疗在老年或体弱CNSL患者中是安全且有效的,可以有效延长其PFS,是一种新的维持治疗选择。     

NLR、LMR水平与转移性结直肠癌维持治疗疗效及预后的相关性

目的:分析转移性结直肠癌维持治疗疗效及预后的相关因素,探讨炎症相关标记物与维持治疗疗效及预后的相关性.方法:筛选131例经标准化疗后缓解或稳定的转移性结直肠癌患者,分析其临床特征,筛选预后相关因子,探讨基线NLR、LMR水平对维持治疗疗效及预后的预测作用.结果:生存分析显示肿瘤分化程度高、基线高NLR、高LMR、低CA19-9水平患者进行维持治疗预后较好;基线高NLR水平维持治疗患者疾病控制率和中位无进展生存期均优于低NLR水平组,基线高LMR水平维持治疗患者的中位无进展生存期优于基线低LMR水平组.结论:肿瘤分化程度、基线NLR、LMR、CA19-9水平可作为转移性结直肠癌维持治疗患者的独立预后因子,基线NLR水平可作为维持治疗的疗效预测因子,基线高NLR水平患者更能从维持治疗中获益.     

Long-term Maintenance Combination Chemotherapy with OPECMPEC (Vincristine or Methotrexate, Prednisolone, Etoposide and Cyclophosphamide) or with Daily Oral Etoposide and Prednisolone Can Improve Survival and Quality of Life in Adult T-cell LeukemiaLymphoma

Acute leukemia and lymphoma varieties of adult T-cell leukemiallymphoma (ATL) usually cany a poor prognosis. While etoposide is generally useful for treating ATL, especially as a daily oral maintenance regimen, etoposide has not proven effective in severe types of ATL efficient in some patients. Of 87 ATL patients whom we have treated, 51 had acute leukemia, 22 lymphoma and 14 progressive chronic leukemia. Seventy-nine patients were treated with a long term maintenance combination rotocol, OPEClMPEC (weekly doses of vincnstine, 0.7 mg/m² or methotrexate, 14 mg/m; prednisolone, 20 mg/m²; etoposide, 70 mg/m² and cyclophosphamide, 200 mg/m²). The other 8 patients, 3 with acute leukemia, 2 with lymphoma and 3 with progressive chronic leukemia, were treated with daily oral administration of 25 mg of etoposide and 10 mg of prednisolone (DOEP). The dose administered was modified in individual cases to maintain the granulocyte count and reduce the number of ATL cells. Considering both protocols, a complete response and a partial response were achieved in 31.0% and 58.6% patients, respectively. Median survival times (MST) of all patients and, acute leukemia, lymphoma and progressive chronic leukemia types were 7.5, 6.7, 9.6 and 12.4 months, respectively. Respective MST of patients treated with OPECNPEC or DOEP protocols were 7.1 and 18.0 months. Relatively normal WBC counts, lower lactate dehydrogenase concentration and normal calcium concentration, limited numbers of anatomic sites involved, good performance status and good response to chemotherapy were significantly associated with long survival time. Drug toxicity was not apparent, and about half of patients were treated in an outpatient setting.     

Phase 2 trial of maintenance bevacizumab alone after bevacizumab plus pemetrexed and carboplatin in advanced,nonsquamous nonsmall cell lung cancer

BACKGROUND:

The authors performed a phase 2 study of bevacizumab plus pemetrexed and carboplatin followed by maintenance bevacizumab in patients with advanced, nonsquamous nonsmall cell lung cancer.

METHODS:

Previously untreated patients with advanced, nonsquamous nonsmall cell lung cancer and an Eastern Cooperative Oncology Group performance status of 0 or 1 received bevacizumab 15 mg/kg, pemetrexed 500 mg/m² and carboplatin at an area under the concentration‐time curve of 6 intravenously on day 1 every 21 days. Responding or stable patients who completed 6 cycles then received bevacizumab maintenance every 21 days until disease progression.

RESULTS:

In total, 43 patients (40 who were evaluable for response) were entered on the study. Treatment‐related grade 3/4 toxicities were low and included febrile neutropenia (2%), neutropenia (28%), anemia (18%), thrombocytopenia (11%), hypertension (7%), epistaxis (5%), venous thrombosis (8%), dyspnea (7%), rectovaginal fistula (2.3%), infusion reaction (2%), and cerebrovascular event (2%). One patient died from complications of venous thromboembolism and cerebrovascular accident after Cycle 2. Minimal clinically significant toxicity occurred during maintenance bevacizumab. Two complete responses (5%) were observed, and 17 patients (42%) had a partial response. Fifteen patients (38%) displayed disease stability. The overall disease control rate was 85%. At a median follow‐up of 15.8 months, the median progression‐free survival was 7.1 months (95% confidence interval, 5.9‐8.3 months), and the median overall survival was 17.1 months (95% confidence interval, 8.8‐25.5 months).

CONCLUSIONS:

Combined bevacizumab, pemetrexed, and carboplatin followed by maintenance bevacizumab was well tolerated and displayed remarkable activity in patients with previously untreated, advanced, nonsquamous nonsmall cell lung cancer. Cancer 2012. © 2012 American Cancer Society.