J R Germà

Institut Català d'Oncologia, Barcino, Catalonia, Spain

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Publications (57)286.41 Total impact

  • European Urology 12/2014; DOI:10.1016/j.eururo.2014.11.041 · 12.48 Impact Factor
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    ABSTRACT: We aimed to analyze prognostic factors for relapse in stage I seminoma managed by either active surveillance or adjuvant chemotherapy, and to describe the long-term patterns of recurrence in both groups.
    Annals of Oncology 09/2014; 25(11). DOI:10.1093/annonc/mdu437 · 6.58 Impact Factor
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    ABSTRACT: Background: Based on the TROPIC study results, cabazitaxel was approved for the management of metastatic castration-resistant prostate cancer (mCRPC) progressing on or after docetaxel.Methods: This multi-centre program provided early access to cabazitaxel to patients with mCRPC before its commercialization. Safety data from 153 Spanish patients receiving cabazitaxel 25 mg/m2 i.v. Q3W, plus oral prednisone/prednisolone 10 mg daily, are reported.Results: Median age of patients was 70 years (26.8% ≥ 75 years), 94.1 and 26.8% had bone and visceral metastasis, respectively. Most had an Eastern Cooperative Oncology Group ≤ 1 (88.9%) and had received a median of 8.0 cycles of last docetaxel treatment. The median of cabazitaxel cycles and cumulative dose were 6.0 (Interquartile range [IQR]: 4.0; 8.0) and 148.9 (IQR: 98.2; 201.4) mg/m2, respectively. Adverse events (AEs) possibly related to cabazitaxel occurred in 143 (93.5%) patients. The most frequent grade ≥ 3 AEs were neutropenia (n = 25, 16.3%) and asthenia (n = 17, 11.1%). Febrile neutropenia and grade ≥ 3 diarrhea occurred in 5.2% of the patients each. There were five (3.3%) possibly treatment-related deaths, mainly infection-related. G-CSFs were used in 114 (74.5%) patients, generally as prophylaxis (n = 107; 69.9%). Grade ≥ 3 peripheral neuropathy and nail disorders were uncommon.Conclusions: Cabazitaxel administration, in a real-world setting, is tolerated by Spanish patients with mCRPC, and the AEs are manageable.
    Expert Opinion on Drug Safety 07/2014; 13(9). DOI:10.1517/14740338.2014.939583 · 2.74 Impact Factor
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    ABSTRACT: We examined whether PI3K-AKT or ERK signaling pathways could play a role in the development of cisplatin (CDDP) resistance in testicular germ cell tumor cells. We compared AKT and ERK activation levels in CDDP-sensitive testicular tumor cells and in their corresponding CDDP-resistant derived cells. We also analyzed these pathways in orthotopic testicular tumors and human patient samples. Our results indicated that there was overactivation of AKT in CDDP-resistant cells compared with sensitive cells, but no effect on activated ERK levels. We observed an increase in mRNA and protein levels for PDGF receptor β and PDGF-B ligand levels. These were responsible for AKT overactivation in CDDP-resistant cells. When PDGFRβ levels were decreased by shRNA treatment or its activation was blocked by pazopanib, CDDP-resistant cells behaved like sensitive cells. Moreover, CDDP-resistant cells were more sensitive to incubation with PDGFRβ inhibitors such as pazopanib or sunitinib than sensitive cells, a finding consistent with these cells being dependent on this signaling pathway. We also found overexpression of PDGFRβ and pAKT in CDDP-resistant choriocarcinoma orthotopic tumor versus their CDDP-sensitive counterparts. Finally, we found high PDGFRβ levels in human testicular tumors, and overexpression in CDDP-resistant testicular choriocarcinomas compared with the CDDP-sensitive and non-treated tumors. The PDGFRβ-AKT pathway plays a critical role in the development of CDDP resistance in testicular tumoral cells.
    Clinical Cancer Research 11/2013; 20(3). DOI:10.1158/1078-0432.CCR-13-1131 · 8.19 Impact Factor
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    ABSTRACT: Cisplatin (CDDP) resistance in testicular germ cell tumors (GCTs) is still a clinical challenge, and one associated with poor prognosis. The purpose of this work was to test pazopanib, an anti-tumoral and anti-angiogenic multikinase inhibitor, and its combination with lapatinib (an anti-ErbB inhibitor) in mouse orthotopic models of human testicular GCTs. We used two different models of human testicular GCTs orthotopically grown in nude mice; a CDDP-sensitive choriocarcinoma (TGT38) and a new orthotopic model generated from a metastatic GCT refractory to first-line CDDP chemotherapy (TGT44). Nude mice implanted with these orthotopic tumors were treated with the inhibitors and the effect on tumoral growth and angiogenesis was evaluated. TGT44 refractory tumor had an immunohistochemical profile similar to the original metastasis, with characteristics of yolk sac tumor. TGT44 did not respond when treated with cisplatin. In contrast, pazopanib had an anti-angiogenic effect and anti-tumor efficacy in this model. Pazopanib in combination with lapatinib in TGT38, an orthotopic model of choriocarcinoma had an additive effect blocking tumor growth. We present pazopanib as a possible agent for the alternative treatment of CDDP-sensitive and CDDP-refractory GCT patients, alone or in combination with anti-ErbB therapies.
    BMC Cancer 08/2013; 13(1):382. DOI:10.1186/1471-2407-13-382 · 3.32 Impact Factor
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    International Journal of Cancer 01/2013; 2013 Jan 7. doi: 10.1002/ijc.28009. [Epub ahead of print]. · 5.01 Impact Factor
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    ABSTRACT: Aim:  Adjuvant 5-flourouracil based chemotherapy has demonstrated benefit in stage III colon cancer (CC) but still remains controversial in stage II. The aim of this study was to analyse the prognostic impact of clinico-pathological factors that may help guide treatment decisions in stage II CC. Method:  Between 1996 and 2006 data from patients diagnosed with colorectal cancer at Hospital Universitari Bellvitge (HUB) and its referral comprehensive cancer center, Institut Català d'Oncologia (ICO)/ L'Hospitalet, were prospectively included in a database. We identified 432 patients with stage II CC operated at HUB. 5-year relapse free survival (RFS) and colon cancer specific survival (CCSS) were determined. Results:  5-year RFS and CCSS were 83% and 88%, respectively. Lymphovascular or perineural invasion was associated with RFS (HR of 1.84; 95% CI, 1.01-3.35). Gender (women HR of 0.48; 95% CI, 0.23-1) and lymphovascular or perineural invasion (HR 3.51; 95% CI, 1.86-6.64), along with pT4 (HR 2.79; 95% CI, 1.44-5.41) influenced CCSS. In multivariate analysis pT4 and lymphovascular or perineural invasion remained significantly associated with CCSS. We performed a risk index with those factors with prognostic impact. Patients with pT4 tumours and lymphovascular or perineural invasion had a 5-year CCSS of 61%, versus the 93% (HR 5.87; 95 CI, 2.46-13.97) of those without any of these factors. Conclusion:  pT4 and lymphatic, venous, or perineural invasion are confirmed as significant prognostic factors in stage II CC and should be taken into account in the clinical validation process of new molecular prognostic factors. © 2012 The Authors Colorectal Disease © 2012 The Association of Coloproctology of Great Britain and Ireland.
    Colorectal Disease 09/2012; 15(4). DOI:10.1111/codi.12028 · 2.02 Impact Factor
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    ABSTRACT: In this work we have analyzed the expression of different members of the ErbB family in human samples of germ-cell testicular tumors (GCTs). We observed expression of ErbB1 or ErbB2 in different tumor subtypes, but we also found high expression of ErbB3 in all GCTs tested. This pattern of expression was maintained when primary tumors were orthotopically implanted in nude mice. We have chosen a choriocarcinoma model characterized by high levels of ErbB1, but also of ErbB2 and ErbB3, to assay the in vivo effect of ErbB inhibitors on tumoral growth. Our results showed a complete lack of effect (refractoriness) to the pure ErbB1 receptor inhibitors cetuximab and gefitinib. While these inhibitors blocked ErbB1 phosphorylation, ErbB2 phosphorylation was not affected, suggesting an ErbB1-independent activation of this receptor. In order to confirm the importance of ErbB2 activation, animals were treated with lapatinib, a dual ErbB1 and ErbB2 inhibitor. Lapatinib treatment caused a 50% inhibition in tumor growth, an effect correlated with a blockade of both ErbB1 and ErbB2 phosphorylation levels, and of downstream signalling pathways (Akt, ERKs and Stat3). ErbB2 activation could still occur due to the formation of ErbB2/ErbB3 heterodimers, and ErbB3 activation was completely inhibited by lapatinib. Finally, combined inhibition of ErbB1 (gefitinib) and ErbB3 activities (knockdown expression by shRNA) inhibited tumoral testicular cells proliferation in a similar way to lapatinib. Our results explain why lapatinib but not anti-ErbB1 agents might be effective for treatment of GCT patients. © 2012 Wiley Periodicals, Inc.
    International Journal of Cancer 07/2012; 48. DOI:10.1002/ijc.28009 · 6.20 Impact Factor
  • European Journal of Cancer 07/2012; 48:S216-S217. DOI:10.1016/S0959-8049(12)71526-5 · 4.82 Impact Factor
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    ABSTRACT: To confirm the efficacy of a risk-adapted treatment approach for patients with clinical stage I seminoma. The aim was to reduce both the risk of relapse and the proportion of patients receiving adjuvant chemotherapy while maintaining a high cure rate. From 2004 to 2008, 227 patients were included after orchiectomy in a multicenter study. Eighty-four patients (37%) presented no local risk factors, 44 patients (19%) had tumors larger than 4 cm, 25 patients (11%) had rete testis involvement, and 74 patients (33%) had both criteria. Only the latter group received two courses of adjuvant carboplatin, whereas the rest were managed by surveillance. After a median follow-up time of 34 months, 16 relapses (7%) have been documented (15 [9.8%] among patients on surveillance and one [1.4%] among those treated with carboplatin). All relapses occurred in retroperitoneal lymph nodes, except for one case in pelvic nodes. Median node size was 25 mm, and median time to recurrence was 14 months. All patients were rendered disease-free with chemotherapy. The actuarial 3-year disease-free survival rate was 88.1% (95% CI, 82.3% to 93.9%) for patients on surveillance and 98.0% (95% CI, 94.0% to 100%) for those treated with adjuvant chemotherapy. Overall 3-year survival was 100%. With the limitations of the short follow-up duration, we confirm that a risk-adapted approach is effective for stage I seminoma. Adjuvant carboplatin seems adequate treatment for patients with 2 risk criteria, as is active surveillance for those with 0 to one risk factors. More reliable predictive factors are needed to improve the applicability of this model.
    Journal of Clinical Oncology 12/2011; 29(35):4677-81. DOI:10.1200/JCO.2011.36.0503 · 17.88 Impact Factor
  • Jorge Aparicio, Javier Sastre, José Ramón Germà, Dolores Isla
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    ABSTRACT: Testicular cancer represents the most common malignancy in males aged 15-34 years. Nearly 40% of cases correspond to seminomas and three quarters of them are diagnosed with stage I disease. After orchiectomy, clinical staging should include serial tumour marker assays (alphafetoprotein must be negative), abdominal CT scan and chest X-ray films. Patients with stage I disease can be followedup (active surveillance) or receive adjuvant carboplatin chemotherapy (those with rete testis invasion or non-compliant with follow-up). More advanced disease (stage II and III) and patients with extragonadal seminomas should receive chemotherapy (3-4 courses of BEP) according to IGCCCG risk classification. Residual lesions must be managed by surveillance if they are smaller than 3 cm, while those larger than 3 cm should be evaluated by means of PET. Surgery is only recommended in PET-positive lesions.
    Clinical and Translational Oncology 08/2011; 13(8):560-4. DOI:10.1007/s12094-011-0697-7 · 1.28 Impact Factor
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    Annals of Oncology 02/2010; 21(2):195-8. DOI:10.1093/annonc/mdp595 · 6.58 Impact Factor
  • 04/2009; 2(2):174-183. DOI:10.1179/175330309791011127
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    ABSTRACT: To provide an outpatient facility to improve the management of chemotherapy toxicity in cancer patients. We set up an oncology acute toxicity unit (OATU) to improve toxicity management. A telephone helpline was the initial contact which filters out inappropriate non-toxicity-related events. Patients were provided an information booklet describing the possible side effects of the chemotherapy and the helpline telephone number. A specialist nurse received the calls and consulted the doctor if necessary. Depending on requirements, the patient's problem was resolved by telephone, or a consultation visit at the OATU was arranged. Between February 1999 and August 2001, 1126 patients made 2007 contacts with the OATU. The most common tumours were breast (26%), colorectal (20%) and lung (20%). The telephone helpline was used in 87% of contacts and 37% were considered inappropriate. Of the 1263 appropriate contacts, the most frequent chemotherapy schedules that had been administered were 5FU-leucovorin (11.2%) and CMF (10.4%). The most frequent side effects were fever (35.5%), diarrhoea (18.5%), mucositis (16.2%) and emesis (13%). The problem was resolved by telephone in 48% of cases and 52% required attendance in the OATU, of which 40% required hospital admission, i.e., 21.1% of the initial appropriate helpline contacts. The most frequent reason was Grade 3-4 neutropenic fever (56.5%). The OATU enables prompt and efficient access of patients to medical oncology facilities in the event of toxicity due to chemotherapy. Unnecessary emergency room use is avoided while oncology outpatient and hospitalisation facilities are optimised.
    Clinical and Translational Oncology 12/2008; 9(12):784-8. DOI:10.1007/s12094-007-0140-2 · 1.60 Impact Factor
  • B Laquente, F Viñals, J R Germà
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    ABSTRACT: Conventional cytotoxic anticancer chemotherapeutic drugs were developed with the intent of treating cancer by direct killing or inhibition of growth of cycling tumour cells. Recently, however, there has been considerable interest in the notion of exploiting such drugs as angiogenesis inhibitors. The rationale is based on the fact that virtually all classes of cancer chemotherapeutic drugs are designed to damage DNA or disrupt microtubules of dividing cells, and endothelial cell division takes place during new blood vessel formation, including tumour angiogenesis. The results of recent experimental studies have suggested that frequent administration of certain cytotoxic agents at low doses, known as "metronomic chemotherapy", increases the putative antiangiogenic activity of certain drugs. Metronomic chemotherapy refers to the chronic administration of comparatively low doses of cytotoxic drugs at close, regular intervals, with no prolonged drug-free interruptions. The advantage of this strategy is lower toxicity and risk of emergence of drug-resistant tumour cells than conventional administration. This review describes the possible antiangiogenesis basis of this therapeutic strategy, the experimental studies published and the recent clinical studies that explore this less toxic schedule.
    Clinical and Translational Oncology 03/2007; 9(2):93-8. DOI:10.1007/s12094-007-0018-3 · 1.60 Impact Factor
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    Jorge Aparicio, José R Germà
    Journal of Clinical Oncology 08/2006; 24(21):e40. DOI:10.1200/JCO.2006.05.7802 · 17.88 Impact Factor
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    ABSTRACT: We previously described Ad-Delta24RGD as an enhanced-infectivity oncolytic adenovirus that targets tumors with an impaired RB pathway. The common alteration of this pathway in cancer eliminates the interaction of pRB with E2F and releases free E2F to activate E2F-responsive promoters, including the E2F-1 promoter. To improve the selectivity towards RB pathway-defective tumors and reduce the toxicity of Ad-Delta24RGD we aimed to control E1A-Delta24 expression under the E2F-1 promoter. A polyA signal was inserted upstream of the E2F-1 promoter to stop transcription initiated at the adenovirus ITR and packaging signal. The human myotonic dystropy locus insulator (DM-1) was also located between the E1a enhancers and the E2F-1 promoter to further insulate the promoter. The Ad-Delta24RGD derivative containing these insulation sequences expressed less E1a-Delta24 in normal cells and resulted less toxic while maintaining the potent oncolytic activity of the parental virus. These results demonstrate that the human DM-1 inslulator can function in an adenovirus context to maintain heterologous promoter selectivity. The new oncolytic adenovirus presented here may represent a valuable therapeutic option for a broad range of tumors with a deregulated E2F/pRB pathway.
    Cancer Gene Therapy 08/2006; 13(7):696-705. DOI:10.1038/sj.cgt.7700940 · 2.55 Impact Factor
  • Jorge Aparicio, J R Germà
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    ABSTRACT: More than a half of patients with testicular cancer are diagnosed with clinical stage I disease. In this setting, definitive cure is the rule. However, there is no consensus on the optimal treatment choice. A literature review (1990-2005) was performed in order to identify the pros and the cons associated with each therapy, as well as their long-term outcomes. Several treatment alternatives yield similar efficacy results. Thus, therapy-related morbidity, economic costs, quality-of-life issues, and patient preferences should be considered. Refinement in the knowledge of predictive factors for relapse and amounting experience with both surveillance and adjuvant chemotherapy have led to consideration of risk-adapted treatment policies as an alternative to more traditional approaches (i.e., prophylactic irradiation for seminomas and retroperitoneal lymph node dissection for non-seminomas). In conclusion, with cure rates approaching 100%, close surveillance for low-risk patients and adjuvant chemotherapy for those at high risk of relapse seems the preferred option for clinical stage I testicular cancer, in both seminoma and non-seminoma cases.
    Medical Oncology 02/2006; 23(3):305-15. DOI:10.1385/MO:23:3:305 · 2.06 Impact Factor
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    ABSTRACT: To assess the efficacy of a risk-adapted treatment policy for patients with stage I seminoma by using universally accepted risk criteria. Between 1999 and 2003, 314 patients with clinical stage I seminoma after orchiectomy were prospectively included. One hundred patients (31.8%) presented no risk factors and were managed with surveillance. In contrast, 131 patients (41.7%) had tumors larger than 4 cm, 33 patients (10.5%) had rete testis involvement, and 50 patients (15.9%) had both risk factors. All the latter received two courses of adjuvant carboplatin. Chemotherapy was well tolerated, as only 17 patients (7.9%) presented grade 3 to 4 toxicity. Relapses were observed in six patients (6.0%) on surveillance and in seven patients (3.3%) treated with carboplatin (0.8% of tumors larger than 4 cm, 9.1% of those involving the rete testis, and 6.0% of patients with both risk criteria). All were located at the retroperitoneum, except for one at the spermatic cord. Median tumor size was 25 mm (range, 11 to 70 mm), and median time to relapse was 9 months (range, 4 to 28 months). All patients were rendered disease-free with chemotherapy (etoposide plus cisplatin). Median follow-up was 34 months (range, 12 to 72 months). The actuarial 5-year disease-free survival rate was 93.4% for patients on surveillance and 96.2% for patients treated with adjuvant chemotherapy. Overall 5-year survival was 100%. Adjuvant carboplatin is effective in reducing the relapse rate in patients with stage I seminoma and risk factors. A risk-adapted strategy is safe and feasible and should be considered an alternative to systematic approaches, such as irradiation, chemotherapy, or surveillance.
    Journal of Clinical Oncology 01/2006; 23(34):8717-23. · 17.88 Impact Factor
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    British Journal of Cancer 05/2004; 90(8):1688; author reply 1689. DOI:10.1038/sj.bjc.6601769 · 4.82 Impact Factor

Publication Stats

813 Citations
286.41 Total Impact Points

Institutions

  • 1998–2014
    • Institut Català d'Oncologia
      Barcino, Catalonia, Spain
  • 2012
    • IDIBELL Bellvitge Biomedical Research Institute
      Barcino, Catalonia, Spain
  • 2011
    • Hospital Universitari i Politècnic la Fe
      Valenza, Valencia, Spain
  • 2001
    • Catalan Institute of Oncology
      Badalona, Catalonia, Spain
  • 1990
    • Universidad Autónoma de Madrid
      Madrid, Madrid, Spain