New perspectives on Aspersentis Megarhynchus (Acanthocephala: Heteracanthocephalidae) from Notothenia Coriiceps Richardson (Nototheniidae) in the West Antarctic, with emended generic diagnosis.

A number of variable descriptive accounts of Aspersentis megarhynchus (von Linstow, 1892) Golvan, 1960 have been reported from specimens collected from many species of fish in various locations off Antarctic islands. We have described a new population from Notothenia coriiceps Richardson (Nototheniidae) off Galindez Island, West Antarctica, and features not previously reported, resolved the taxonomic controversies and nomenclature, and emended and updated the generic diagnosis taking into account the newly observed structures. These are depicted in microscopic images and include the outer spiral wall of the proboscis receptacle, the thicker dorsal wall of the receptacle compared to the ventral wall, parts of the female reproductive system, the separate cement gland ducts, the dorsal position of the male gonopore and more detail of proboscis hooks and trunk spines. It is surprising that the newly observed features were missed from the many descriptions of A. megarhynchus created since the original description. The variability in A. megarhynchus is noted with a comparison of the morphometrics of our specimens vs. those in six other descriptions. We also analysed the metal composition of hooks and spines using energy-dispersive X-ray analysis and concluded a molecular characterization of the species based on 18S DNA gene, with related phylogenetic analyses.

Description and molecular analysis of an Italian population of Centrorhynchus globo caudatus (Zeder, 1800) Lühe, 1911 (Acanthocephala: Centrorhynchidae) from Falco tinnunculus (Falconidae) and Buteo buteo (Accipitridae).

Centrorhynchus globocaudatus (Zeder, 1800) Lühe, 1911 (Centrorhynchidae) was reported in birds of prey. Our population from Falco tinnunculus Linnaeus (Falconidae) and Buteo buteo Linnaeus (Accipitridae) in northern Italy was morphologically distinct from others described elsewhere. The worms are elongate and cylindrical. Proboscis long, apically truncated and bare, with wider base and variably faint constriction at point of attachment of receptacle. Large anterior hooks well rooted; posterior spiniform hooks with reduced roots; transitional hooks with scutiform roots in-between. Four tubular cement glands extend into prominent ducts overlapping a large Saefftigen's pouch. Bursa large, with sensory plates. Vagina with laterally slit orifice in sub-ventral pit of globular terminal extension. Thick-shelled eggs ovoid without polar prolongation of fertilization membrane. In our specimens, proboscis hooks, receptacle, male reproductive system, and lemnisci especially in males varied in size from those from Ukraine, India, Egypt, Kyrgystan, Russia, Georgia, Armenia and Asian Soviet Republics. Our description of the Italian specimens includes new morphological information supported by scanning electron microscopy and microscope images, molecular analysis and energy dispersive X-ray analysis (EDXA) of hooks. Additional new details of proboscis hook roots, micropores and micropore distribution are described. Metal composition of hooks (EDXA) demonstrated high levels of calcium and phosphorous, and high levels of sulphur in core and cortical layers of eggs. The molecular profile based on sequences of 18S and cytochrome c oxidase 1 genes is also provided, as well as phylogenetic reconstructions including all available sequences of the family Centrorhynchidae, although further sequences are needed in order to clarify their phylogenetic relationships.

BOMET-QoL-10 questionnaire for breast cancer patients with bone metastasis: the prospective MABOMET GEICAM study.

BACKGROUND: Bone metastasis (BM) is the most common site of disease in metastatic breast cancer (MBC) patients. BM impacts health-related quality of life (HRQoL). We tested prospectively the psychometric properties of the Bone Metastasis Quality of Life (BOMET-QoL-10) measure on MBC patients with BM. METHODS: Patients completed the BOMET-QoL-10 questionnaire, the Visual Analogue Scale (VAS) for pain, and a self-perceived health status item at baseline and at follow-up visits. We performed psychometric tests and calculated the effect size of specific BM treatment on patients´ HRQoL. RESULTS: Almost 70% of the 172 patients reported symptoms, 23.3% experienced irruptive pain, and over half were receiving chemotherapy. BOMET-QoL-10 proved to be a quick assessment tool performing well in readability and completion time (about 10 min) with 0-1.2% of missing/invalid data. Although BOMET-QoL-10 scores remained fairly stable during study visits, differences were observed for patient subgroups (e.g., with or without skeletal-related events or adverse effects). Scores were significantly correlated with physician-reported patient status, patient-reported pain, symptoms, and perceived health status. BOMET-QoL-10 scores also varied prospectively according to changes in pain intensity. CONCLUSIONS: BOMET-QoL-10 performed well as a brief, easy-to-administer, useful, and sensitive HRQoL measure for potential use for clinical practice with MBC patients. TRIAL REGISTRATION: NCT03847220. Retrospectively registered on clinicaltrials.gov (February the 20th 2019).

Horizontal transmission of Endolimax piscium, causative agent of systemic amoebiasis in Senegalese sole Solea senegalensis.

Systemic amoebiasis of Senegalese sole Solea senegalensis is caused by Endolimax piscium Constenla, Padrós & Palenzuela, 2014 a cryptic parasitic member of the Archamoebae whose epidemiology is yet unknown. To test whether the parasite can be transmitted horizontally, an experimental trial by cohabitation between non-infected and infected fish was designed. Transmission of the parasite from naturally infected to healthy fish was confirmed in the experiment, with the water as the most likely route of infection. Under the conditions of the study, the infection process was remarkably slow, as parasites could be detected by in situ hybridization within the intestinal mucosa of recipient fish only after 17 wk of cohabitation, and none of the new hosts displayed clinical signs of disease. Long prepatent period and the need for additional triggering factors for the development of the clinical condition are suggested. The intestinal mucosa is proposed as the tissue where the amoeba can survive as endocommensal, but also as an invasion route from which the parasite would disperse to other organs.

Comparison of plasma ctDNA and tissue/cytology-based techniques for the detection of EGFR mutation status in advanced NSCLC: Spanish data subset from ASSESS.

PURPOSE: The analysis of epidermal growth factor receptor (EGFR) mutations in many patients with advanced non-small-cell lung cancer (aNSCLC) has provided the opportunity for successful treatment with specific, targeted EGFR tyrosine kinase inhibitors. However, this therapeutic decision may be challenging when insufficient tumor tissue is available for EGFR mutation testing. Therefore, blood surrogate samples for EGFR mutation analysis have been suggested. METHODS: Data were collected from the Spanish cohort of patients in the large, non-interventional, diagnostic ASSESS study (NCT01785888) evaluating the utility of circulating free tumor-derived DNA from plasma for EGFR mutation testing. The incidence of EGFR mutation in Spain and the level of concordance between matched tissue/cytology and plasma samples were evaluated. RESULTS: In a cohort of 154 eligible patients, EGFR mutations were identified in 15.1 and 11.0% of tumor and plasma samples, respectively. The most commonly used EGFR mutation testing method for the tumor tissue samples was the QIAGEN Therascreen® EGFR RGQ PCR kit (52.1%). Fragment Length Analysis + PNA LNA Clamp was used for the plasma samples. The concordance rate for EGFR mutation status between the tissue/cytology and plasma samples was 88.8%; the sensitivity was 45.5%, and the specificity was 96.7%. CONCLUSIONS: The high concordance between the different DNA sources for EGFR mutation testing supports the use of plasma samples when tumor tissue is unavailable.

Galician consensus on management of cardiotoxicity in breast cancer: risk factors, prevention, and early intervention.

This Galician consensus statement is a joint oncologists/cardiologists initiative indented to establish basic recommendations on how to prevent and to manage the cardiotoxicity in breast cancer with the aim of ensuring an optimal cardiovascular care of these patients. A clinical screening of the patients before treatment is recommended to stratify them into a determined risk group based on their intrinsic cardiovascular risk factors and those extrinsic arose from breast cancer therapy, thereby providing individualized preventive and monitoring measures. Suitable initial and ongoing assessments for patients with low and moderate/high risk and planned treatment with anthracyclines and trastuzumab are given; also, measures aimed at preventing and correcting any modifiable risk factor are pointed out .

Development of different diagnostic techniques for Endolimax piscium (archamoebae) and their applicability in Solea senegalensis clinical samples.

Systemic amoebiasis of sole is caused by Endolimax piscium, a cryptic parasitic archamoeba whose epidemiology and pathogeny are yet unknown. To establish reliable detection methods for this parasite, a battery of molecular diagnostic tools (ISH, PCR and qPCR) were developed and evaluated with a panel of clinical samples from symptomatic diseased fish and from apparently normal animals of different stocks. As there is neither enough background information on the epidemiology of the disease nor a validated reference method, comparison of tests used a composite reference method approach. The ISH technique was the most specific and sensitive in intestine samples and particularly useful as a reference confirmatory method, while the best method in muscle samples was qPCR. Application of the tests to asymptomatic fish demonstrated presence of parasites in a large proportion (>25%) of their intestines, suggesting that this is the point of entry of the amoebae and the initial stage in the development of the disease. The triggering factors that facilitate the breaching of the intestinal barrier by E. piscium, causing granulomatous lesions in other organs and systemic spreading, are not completely understood but our results point to the connective tissue as a preferential target for parasite development and migration.

Endolimax piscium sp. nov. (Amoebozoa), causative agent of systemic granulomatous disease of cultured sole, Solea senegalensis Kaup.

A new amoeba species pathogenic for Senegalese sole is described based on ultrastructural analysis and SSU rDNA phylogenetic inference. The parasite presents round to ovoid trophozoites (<5 µm) with a high degree of intracellular simplification. No mitochondria were observed, but mitosome-like organelles were present. No cysts could be detected. Phylogenetic analysis confirmed the Senegalese sole parasite as an amitochondriate Archamoeba related to Endolimax nana and Iodamoeba spp., and we tentatively describe it as a new species in the genus Endolimax, Endolimax piscium. However, the genetic distance with E. nana is quite large, with only 60% pairwise identity between both SSU rDNA genotypes. Although the overall topology of the Archamoebae cladograms containing E. piscium was consistent, the support for the branching of Endolimax spp. relative to its closest neighbours was variable, being higher with distance or parsimony-based inference methods than with ML or Bayesian trees. The use of stringent alignment sampling masks also caused instability and reduced support for some branches, including the monophyly of Endolimax spp. in the most conservative data sets. The characterization of other Archamoebae parasitizing fish could help to clarify the status of E. piscium and to interpret the large genetic distance observed between Endolimax species.

Panitumumab and irinotecan every 3 weeks is an active and convenient regimen for second-line treatment of patients with wild-type K-RAS metastatic colorectal cancer.

PURPOSE: To evaluate the efficacy and safety profile of the combination of panitumumab and irinotecan every 3 weeks in a phase II trial as second-line treatment in patients with advanced wild-type (WT) K-RAS colorectal cancer (CRC). METHODS: Fifty-three patients received 9 mg/kg of panitumumab followed by 350 mg/m(2) of irinotecan every 21 days until disease progression, unacceptable toxicity or consent withdrawal. RESULTS: Median age of patients included was 67 years. All patients had previously received 5-fluorouracil, 84 % oxaliplatin and 8 % irinotecan as first-line treatment. Patients received a median of five infusions of panitumumab and irinotecan. On an intention-to-treat analysis, 12 patients (23 %) achieved partial responses and 22 patients (41 %) achieved disease stabilization. Median progression-free survival and overall survival were 4.5 and 15.1 months, respectively. The most frequent treatment-related severe toxicities per patient were diarrhoea (35.8 %), followed by skin rash (32.1 %), asthenia (18.9 %) and neutropenia (13.2 %). A significant association between clinical response and incidence and grade of skin toxicity was observed (p = 0.0032). CONCLUSION: This study shows that the administration of panitumumab plus irinotecan every 3 weeks is safe, active and feasible as second-line treatment in patients with advanced WT K-RAS CRC.

Parasitisation by Bathycreadium elongatum (Digenea, Opecoelidae) in pyloric caeca of Trachyrincus scabrus (Teleostei, Macrouridae).

A novel process of transmural passive displacement of a digenean parasite was studied in the digestive tract of the roughsnout grenadier Trachyrincus scabrus, which is found in the northwestern Mediterranean Sea. This mechanism seems to facilitate the elimination of a significant portion of intestinal parasites. The digenean parasite Bathycreadium elongatum was found in the intestine, mainly within pyloric caeca, in 74.4% of T. scabrus, with a mean abundance of 44 individuals per fish. Nodule-like lesions were also found in the mesentery of pyloric caeca of infected T. scabrus. Histological sections of the nodules revealed granulomatous inflammatory responses surrounding degraded digeneans. Partial nucleotide sequences of the 28S rRNA gene obtained from intracaecal B. elongatum and from the core of the nodules of the mesentery of pyloric caeca showed 100% mutual identity with an overlap of 971 bp. The greatest abundance of both intracaecal B. elongatum and nodules occurred in spring. During summer, and especially autumn, the abundance of intracaecal B. elongatum decreased. Prevalence and abundance of nodules increased in autumn. In winter intracaecal parasite abundance and prevalence began to increase, but decreased again in nodules. During spring and summer, parasites pass into the visceral cavity, hypothetically owing to the fragility of the wall of pyloric caeca in their apical zone, and become degraded through a granulomatous inflammatory response. This process seems to have a detrimental effect on the B. elongatum cycle since some of parasites are trapped and degrade in the connective tissue in which they are unable to complete their life cycle.

Histopathological and ultrastructural studies on a novel pathological condition in Solea senegalensis.

A new parasitic disease affecting cultured sole Solea senegalensis (Kaup, 1858) is characterised by the presence of external protuberances in the skin of the affected fish. These lesions correspond to nodules in the muscular tissue showing an abscess-like aspect. Similar lesions were found in the kidney, heart, liver and digestive tract. Histological sections of these nodules revealed the presence of a large core formed mainly of necrotic tissue surrounded with fibroblasts and macrophages. Round-shaped plasmodial organisms were found in the external layer of the nodules and usually inside macrophages or fibroblasts. These organisms were also observed in the intestinal mucosa inside phagocytic cells or parasitophorous vacuoles within the enterocytes. The morphological and ultrastructural characteristics of these organisms are similar to the morphology of some groups of parasites described as fish pathogens. The main features suggest that these organisms could be amoebae or parasites with an amoeboid or plasmodial form in their developmental cycle.

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.

Randomized phase II study of cetuximab plus cisplatin/vinorelbine compared with cisplatin/vinorelbine alone as first-line therapy in EGFR-expressing advanced non-small-cell lung cancer.

BACKGROUND: The Lung Cancer Cetuximab Study is an open-label, randomized phase II pilot study of cisplatin and vinorelbine combined with the epidermal growth factor receptor (EGFR)-targeted monoclonal antibody cetuximab versus cisplatin and vinorelbine alone, in patients with advanced EGFR-expressing, non-small-cell lung cancer (NSCLC). End points of the study are activity, safety and pharmacokinetics. PATIENTS AND METHODS: Following randomization, for a maximum of eight cycles, patients received three-weekly cycles of cisplatin (80 mg/m(2), day 1) and vinorelbine (25 mg/m(2) on days 1 and 8) alone or following cetuximab treatment (initial dose 400 mg/m(2), followed by 250 mg/m(2) weekly thereafter). RESULTS: Eighty-six patients were randomly allocated to the study (43 per arm). Confirmed response rates were 28% in the cisplatin/vinorelbine arm (A) and 35% in the cetuximab plus cisplatin/vinorelbine arm (B). Median progression-free survival (PFS) was 4.6 months in arm A and 5.0 months in arm B, with PFS rates at 12 months of 0% and 15%, respectively. Median survival was 7.3 months in arm A and 8.3 months in arm B. The 24-month survival rates were 0% and 16%, respectively. The cetuximab combination was well tolerated. CONCLUSION: In the first-line treatment of advanced NSCLC, the combination of cetuximab plus cisplatin/vinorelbine demonstrated an acceptable safety profile and the potential to improve activity over cisplatin/vinorelbine alone.

Pegfilgrastim supports delivery of FEC-100 chemotherapy in elderly patients with high risk breast cancer: a randomized phase 2 trial.

This randomized phase 2 study explored the feasibility of delivering four to six cycles of the dose-intensified regimen FEC-100 (5-fluorouracil, epirubicin, and cyclophosphamide) to elderly patients with stage II-III breast cancer, using pegfilgrastim for neutrophil support. Sixty patients aged 65-77 years received single 6mg doses of pegfilgrastim on day 2 of FEC-100, either as primary prophylaxis (all cycles: PP), or as secondary prophylaxis (all cycles following a neutropenic event: SP). Neutropenic events (a composite endpoint that included grade 3 neutropenia+fever, grade 4 neutropenia, infectious complication requiring systemic anti-infectives and chemotherapy dose delay/reduction) occurred in 24/30 (80%) of the PP and 21/29 (72%) of the SP group in the first cycle. Most patients received all chemotherapy cycles at full dose on schedule (26/30 [87%] PP; 20/29 [69%] SP). These data indicate that delivery of FEC-100 is feasible with pegfilgrastim support in elderly breast cancer patients.

A retrospective analysis of the outcome of patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck refractory to a platinum-based chemotherapy.

AIMS: Recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) develops in around 72,000 people in Europe every year. Treatment options are limited, mainly consisting of platinum-based palliative chemotherapy, with median overall survival times of only 6-8 months. No standard second-line treatment after progression on platinum-based chemotherapy is available. Few data have reported the efficacy of these treatments and the outcome of the patients. In an effort to generate such data, this retrospective study analysed clinical records from 151 patients with SCCHN refractory to platinum-based chemotherapy treated between 1990 and 2000 at seven different centres around Europe. MATERIALS AND METHODS: Most patients (45%) received only best supportive care (BSC), and had a median survival of 56 days. A total of 28.5% of the patients received second-line chemotherapies: 16.6% radiotherapy and 9.9% chemoradiotherapy. RESULTS: No objective response was observed with the various second-line chemotherapies. The overall median survival was 103 days (95% confidence interval [CI]: 77-126 days) for the whole cohort. The overall objective response rate (ORR) to second-line treatment in this population was calculated to be 2.6%. CONCLUSION: These results highlight the need for additional treatment options for this disease. Similar, if not superior, response rates have already been observed in initial clinical studies of novel, targeted anti-cancer agents.

Sequential mitoxantrone/prednisone followed by docetaxel/estramustine in patients with hormone refractory metastatic prostate cancer: results of a phase II study.

BACKGROUND: Mitoxantrone/prednisone ameliorates symptoms in hormone refractory prostate cancer (HRPC) but has no effect on survival. Docetaxel (Taxotere)/estramustine improves response but with significant toxicity. We reasoned that a sequential administration of the two regimens could be a viable alternative for delivering full doses of chemotherapy, avoiding overlapping toxicity and preserving dose intensity. PATIENTS AND METHODS: Thirty HRPC patients were treated with mitoxantrone 10 mg/m(2), day 1, every 3 weeks, plus prednisone 5 mg twice daily, for three cycles, followed by estramustine phosphate, 280 mg three times daily, days 1 to 5, plus docetaxel 75 mg/m(2), day 2, every 3 weeks for a maximum of 10 cycles. RESULTS: All patients were assessable for response and toxicity. After mitoxantrone/prednisone treatment, the prostate-specific antigen (PSA) response rate was 23%, which increased to 63% after completion of sequential mitoxantrone/prednisone and docetaxel/estramustine treatment (12 partial and 7 complete responses). With a median follow-up of 18 months, median survival for all patients was 18 months, and median progression-free survival was 10 months. The mitoxantrone/prednisone regimen was well tolerated, and the only grade 3-4 toxicity was grade 3 neutropenia in four (13%) patients. Twenty-nine patients received a total of 173 cycles of docetaxel/estramustine (median, 6 cycles/patient). Six (20%) patients had grade 3-4 neutropenia and two (6%) patients had febrile neutropenia episodes. The most frequent non-hematological toxic effects were asthenia, nausea and vomiting, edemas and onycholysis. Two (6%) patients had deep venous thrombosis. CONCLUSIONS: Mitoxantrone/prednisone followed by docetaxel/estramustine is a well-tolerated and active regimen in HRPC. Sequential therapy is feasible and can be used to integrate novel, more active regimens.

Docetaxel as single-agent treatment in elderly patients with advanced breast cancer.

OBJECTIVE: To assess the efficacy and safety profile of docetaxel, as a single agent, in the treatment of elderly patients with advanced breast cancer. METHODS: Twenty-eight patients, with a median age of 72 (range 66-84) years, were included in the study and received docetaxel (50-100 mg/m(2)) every 3-4 weeks as first- or second-line treatment of advanced breast cancer. Granulocyte colony-stimulating factor (G-CSF) was administered as primary prophylaxis in 97% of cycles. RESULTS: The overall response rate was 50% (95% CI 32, 69). The median time to disease progression was 10.7 months (95% CI 10.0, 11.5), and the median overall survival was 26.6 months (95% CI 16.6, 36.7). Neutropenia was the most frequent grade 3/4 toxicity (18% of patients and 5% of cycles). There was just one case of febrile neutropenia that resulted in toxic death. Severe neutropenia only occurred in patients who did not receive G-CSF support from the start of the study treatment. Vomiting was the most frequent grade 3/4 non-haematological toxicity (11% of patients and 2% of cycles). CONCLUSION: Docetaxel as a single agent is active in elderly patients with advanced breast cancer. The use of prophylactic G-CSF allowed the administration of high doses of docetaxel with minimal myelosuppression.

Phase II study of capecitabine in combination with paclitaxel in patients with anthracycline-pretreated advanced/metastatic breast cancer.

The addition of oral capecitabine to docetaxel improves response rate, time to progression (TTP) and overall survival in anthracycline-pretreated metastatic breast cancer (MBC). This phase II study evaluates the efficacy and safety of a 21-day cycle of oral capecitabine (1000 mg m(-2) twice daily, days 1-14) plus i.v. paclitaxel (175 mg m(-2), day 1) in anthracycline-pretreated advanced/MBC. In all, 73 patients were enrolled at 13 Swedish and Spanish centres. The objective response rate was 52% (95% confidence interval (CI): 40-63%) in the intent-to-treat population, including complete responses in 11%. Disease was stabilised in a further 29%. The median time to disease progression (TTP) was 8.1 months and the median overall survival was 16.5 months. The combination was generally well tolerated with a predictable safety profile. The most common treatment-related nonhaematological adverse events were hand-foot syndrome (42%), alopecia (30%) and diarrhoea (26%). The only treatment-related Grade 3/4 adverse events occurring in >5% of patients were alopecia (22%) and hand-foot syndrome (11%). Grade 3/4 neutropenia and lymphocytopenia were reported in 12 and 14% of patients, respectively. Capecitabine plus paclitaxel is highly active with a favourable safety profile in anthracycline-pretreated MBC.

Phase II study of carboplatin and 1-h intravenous etoposide and paclitaxel in a novel sequence as first-line treatment of patients with small-cell lung cancer.

PURPOSE: To evaluate the efficacy and tolerability of paclitaxel, carboplatin and etoposide when administered in combination to previously-untreated small-cell lung cancer (SCLC) patients. PATIENTS AND METHODS: Patients (n=95) with limited-stage disease (LSD; n=45) or extensive-stage disease (ESD; n=50) from 14 Spanish hospitals were entered into the study. Etoposide was administered 80 mg/m(2)/day intravenous (i.v.) on days 1, 2 and 3, paclitaxel 175 mg/m(2) i.v. on day 3 and carboplatin area-under-the-concentration-time-curve=6; i.v. on day 3, of a 3-week cycle, and repeated for up to 6 cycles. RESULTS: The overall response (OR) rate was 74% (n=70; 32 complete, 38 partial). Although the OR in LSD and ESD patients was similar (73 vs 74%, respectively), the percentage complete response was significantly higher among the former (49 vs 20%). The main toxicities were grade 3-4 neutropenia and febrile neutropenia (62 and 18%, respectively) and there were 3 toxic deaths. Other toxicities were rare or easily manageable. Disease-free survival and overall survival rates at 1 year were 53 and 70% in LSD and 18 and 39% in ESD patients, respectively. CONCLUSION: The results indicate that the combination of paclitaxel, etoposide and carboplatin has an anti-tumour activity in SCLC that is comparable to other combination regimens, and is well tolerated.

Phase II study of irinotecan as first-line chemotherapy for patients with advanced colorectal carcinoma.

BACKGROUND: The objective of this multicenter, open-labeled, Phase II study performed in Spain was to assess the efficacy and safety of irinotecan (CPT-11) as first-line chemotherapy for patients suffering from advanced colorectal carcinoma (CRC). METHODS: Patients with histologically proven CRC and at least one bidimensionally measurable lesion, ages 18-70 years, with a performance status < or = 2, normal analytical values, and no prior chemotherapy or only adjuvant chemotherapy completed before study entry were selected. The treatment schedule was CPT-11 350 mg/m(2) intravenously administered once every 3 weeks. Both tumor response and toxicity were assessed using the World Health Organization and National Cancer Institute common toxicity criteria. Changes in performance status, weight, and symptoms also were measured. RESULTS: Sixty-five patients (44 chemotherapy-naïve patients and 21 patients who completed prior adjuvant treatment) were enrolled. Of these, 24.7% of patients responded to the treatment, and 41.5% of patients had stable disease. Patients who had not received prior adjuvant chemotherapy had a lower rate of progression on therapy (27.3%) compared with those who had received prior adjuvant chemotherapy (42.9%). The median survival was 19.9 months (range, 0.3-29.3 months). No significant differences were found in the median survival between chemotherapy-naïve patients and patients who had received previous chemotherapy. Grade 3-4 diarrhea and neutropenia were the most frequent severe toxic events, which were observed in 23.1% and 30.8% of patients and in 5.9% and 10.9% of the cycles, respectively. CONCLUSIONS: The current antitumor efficacy results show that 350 mg/m(2) of CPT-11 administered every 3 weeks is an active and feasible first-line chemotherapy regimen for patients with CRC. Finally, the overall safety data confirmed that CPT-11 is a well tolerated treatment.