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Vega Iranzo,
Rafael Sirera,
Alfredo Carrato,
Andrea Cabrera,
Eloísa Jantus,
Ricardo Guijarro,
Elena Sanmartín,
Ana Blasco,
Mireia Gil,
Lorenzo Gómez-Aldaraví, José Luis González-Larriba,
Bertomeu Massuti,
Amalia Velasco,
Mariano Provencio,
Rafael Rosell,
Carlos Camps
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ABSTRACT: BackgroundIn advanced-stage (IIIB or IV) non-small-cell lung cancer (NSCLC), combination chemotherapy has demonstrated response rates
of 20% and a 1-year survival rate of 30%. We conducted a multicentre, open-label, nonrandomised phase II trial to determine
the efficacy and tolerability of sequential monotherapy with gemcitabine followed by paclitaxel in chemotherapy-naïve patients
with advanced NSCLC.
Materials and methodsBetween December 2002 and July 2004, the Spanish Lung Cancer Group (SLCG) conducted a study in which 34 patients with advanced
(stage IIIB or IV) NSCLC received 1200 mg/m2 of i.v. gemcitabine on days 1, 8 and 15 of each 28-day cycle for a total of 3 cycles followed by 100 mg/m2 of weekly i.v. paclitaxel for a maximum of 8 weeks. If objective response or stable disease was achieved, 70 mg/m2 of weekly i.v. paclitaxel was maintained until disease progression was evident or toxic effects were intolerable. Lung Cancer
Symptom Scale (LCSS) analysis was performed. Baseline levels of serum VEGF, EGFR, telomerase reverse transcriptase (hTERT)
and K-ras mutations were analysed. The primary endpoint was the objective response rate.
ResultsThe median age of the 34 patients who were enrolled was 67 years (range 46–77), but later 8 patients were excluded; 78.8%
were men, 81.8% had performance status 1 and also 81.8% had metastatic disease at diagnosis. The objective response rate was
28% (95% CI, 14.2–47.8); the median overall survival was 7.2 months (95% CI, 2.1–12.3) and the median time to progression
(TTP) was 3.1 months (95% CI, 2.5–5.3). Grade 3 or 4 drug-related haematological toxicities were observed in 6 patients. Patients
with lower baseline serum VEGF levels had significantly longer survival.
ConclusionsSequential therapy with gemcitabine followed by paclitaxel was well tolerated with a low proportion of grade 3 or 4 adverse
events, the absence of unexpected toxicity and with an improvement in quality of life. Unfortunately, the response rate did
not meet the minimally required rate of 20% and the study was prematurely closed. VEGF was identified as a poor prognostic
factor for TTP and survival.
KeywordsSequential monotherapy–Pharmacogenomics–VEGF–EGFR–hTERT–Non-small-cell lung cancer
Clinical and Translational Oncology 04/2012; 13(6):411-418. · 1.33 Impact Factor
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ABSTRACT: Metastatic renal cell carcinoma is resistant to conventional treatment with chemotherapy. Recently the use of molecular-targeted therapies with multikinase inhibitors has been recommended as first-choice therapy because they inhibit cell proliferation and tumour angiogenesis. Sorafenib is a well tolerated tyrosine kinase inhibitor that initially demonstrated efficacy in the treatment of patients with metastatic RCC who progressed after immunotherapy. Expanded-access studies in Europe and North America showed the safety and efficacy of sorafenib in special populations such as elderly, renal failure and cerebral metastases, as well as patients with no prior therapy. No cross-resistance has been suggested in non-randomized trials when used in second line treatment after other targeted therapies. Ongoing clinical trials will better define the role of sorafenib in first and second line either as monotherapy or in combination, as well as the best strategies for the sequential use of this drug.
Critical reviews in oncology/hematology 03/2011; 80(2):314-22. · 5.27 Impact Factor
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ABSTRACT: The speed at which targeted therapies are being developed and incorporated into the treatment of advanced renal cell carcinoma (RCC) is surprising. After decades in which the only systemic treatment options available for advanced disease were interleukin-2 and interferon-alpha, in the last decade, six new targeted therapies have emerged showing meaningful clinical benefits to patients with advanced RCC through phase III trials. Recently, the Spanish Oncology Genitourinary Group issued its first public statement of recommendations for the optimal management of advanced RCC. However, most pivotal phase III trials on which these recommendations were based have been updated and/or fully reported. Moreover, a new multikinase inhibitor, pazopanib, has emerged with good quality clinical data. In this report, we review in depth the latest phase III data of targeted therapies for advanced RCC and update our recommendations. Furthermore, we hypothesize about the best environment for patients with advanced RCC to receive cancer therapy.
CANCER AND METASTASIS REVIEW 08/2010; 29 Suppl 1:1-10. · 9.35 Impact Factor
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ABSTRACT: Elderly or frail patients are often excluded from clinical trials. As a result, clinical outcome of these patients may differ from those obtained in trials. This situation may also hold true for patients who have severe concomitant diseases such as renal, hepatic, or cardiac dysfunction. Being aware of the wide range of clinical situations that a specialist may face is important to ensure that under any circumstances, the patient will receive the best treatment possible. The Spanish Oncology Genitourinary Group issued its first public statement on recommendations for the optimal management of advanced renal cell carcinoma (RCC). However, some issues remained unsolved. In this report, we discuss the current role of Medical Oncology in the treatment of patients with advanced RCC and review the management of special patient populations, such as elderly or patients with concomitant diseases.
CANCER AND METASTASIS REVIEW 08/2010; 29 Suppl 1:11-20. · 9.35 Impact Factor
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Enriqueta Felip,
Rafael Rosell,
José Antonio Maestre,
José Manuel Rodríguez-Paniagua,
Teresa Morán,
Julio Astudillo,
Guillermo Alonso,
José Manuel Borro, José Luis González-Larriba,
Antonio Torres,
Carlos Camps,
Ricardo Guijarro,
Dolores Isla,
Rafael Aguiló,
Vicente Alberola,
José Padilla,
Abel Sánchez-Palencia,
José Javier Sánchez,
Eduardo Hermosilla,
Bartomeu Massuti
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ABSTRACT: To address whether preoperative chemotherapy plus surgery or surgery plus adjuvant chemotherapy prolongs disease-free survival compared with surgery alone among patients with resectable non-small-cell lung cancer.
In this phase III trial, 624 patients with stage IA (tumor size > 2 cm), IB, II, or T3N1 were randomly assigned to surgery alone (212 patients), three cycles of preoperative paclitaxel-carboplatin followed by surgery (201 patients), or surgery followed by three cycles of adjuvant paclitaxel-carboplatin (211 patients). The primary end point was disease-free survival.
In the preoperative arm, 97% of patients started the planned chemotherapy, and radiologic response rate was 53.3%. In the adjuvant arm, 66.2% started the planned chemotherapy. Ninety-four percent of patients underwent surgery; surgical procedures and postoperative mortality were similar across the three arms. Patients in the preoperative arm had a nonsignificant trend toward longer disease-free survival than those assigned to surgery alone (5-year disease-free survival 38.3% v 34.1%; hazard ratio [HR] for progression or death, 0.92; P = .176). Five-year disease-free survival rates were 36.6% in the adjuvant arm versus 34.1% in the surgery arm (HR 0.96; P = .74).
In early-stage patients, no statistically significant differences in disease-free survival were found with the addition of preoperative or adjuvant chemotherapy to surgery. In this trial, in which the treatment decision was made before surgery, more patients were able to receive preoperative than adjuvant treatment.
Journal of Clinical Oncology 07/2010; 28(19):3138-45. · 18.37 Impact Factor
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ABSTRACT: For almost the last two decades, interleukin-2 and interferon-alpha have been the only systemic treatment options available for metastatic renal cell carcinoma. However, in recent years, five new targeted therapies namely sunitinib, sorafenib, temsirolimus, everolimus and bevacizumab have demonstrated clinical activity in these patients. With the availability of new targeted agents that are active in this disease, there is a need to continuously update the treatment algorithm of the disease. Due to the important advances obtained, the Spanish Oncology Genitourinary Group (SOGUG) has considered it would be useful to review the current status of the disease, including the genetic and molecular biology factors involved, the current predicting models for development of metastases as well as the role of surgery, radiotherapy and systemic therapies in the early- or late management of the disease. Based on this previous work, a treatment algorithm was developed.
Cancer Chemotherapy and Pharmacology 04/2009; 63 Suppl 1:S1-13. · 2.83 Impact Factor
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ABSTRACT: A retrospective analysis based on the Spanish Lung Cancer Group (SLCG) clinical trial of high-dose epirubicin/cisplatin in patients with small-cell lung cancer (SCLC) was performed. Patients younger than 70 years vs. older than 70 years old were analyzed to evaluate the influence of age on response to treatment, toxicity, time to progression (TTP) and overall survival (OS) of the chemotherapy schedule. Three hundred and thirty eight patients <70 years and sixty-four >70 years, were analyzed. Objective responses were similar in both groups. In patients less than 70 years higher TTP (36 weeks vs. 32 weeks) and OS (47 weeks vs. 42 weeks) were seen, attributable to the improved results observed in the subgroup of patients with limited disease (LD). No significant differences were observed when toxicity profile of both groups was compared, except for a higher rate of febrile neutropenia observed in the elderly group with extensive disease (4.6% vs. 8.8%, p=0.01). In the subgroup of patients with LD, elderly patients received less total cisplatin dose (401 vs. 508 mg/m(2), p=0.01) although less treatment delays were reported (10 days vs. 15 days, p=0.05). Age was likely to be a negative prognostic factor for OS of elderly patients with LD. It also seemed to be related to a greater dose reduction, which may explain that toxic episodes and delays occurred more frequently in the younger patients receiving the full scheduled dose. However, the definitive reason to explain this could not be established due to the characteristics of our analysis.
Lung Cancer 06/2008; 63(1):83-7. · 3.43 Impact Factor
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Pilar Garrido, José Luis González-Larriba,
Amelia Insa,
Mariano Provencio,
Antonio Torres,
Dolores Isla,
José Miguel Sanchez,
Felipe Cardenal,
Manuel Domine,
Jose Ramon Barcelo,
Vicente Tarrazona,
Andres Varela,
Rafael Aguilo,
Julio Astudillo,
Ignacio Muguruza,
Angel Artal,
Florentino Hernando-Trancho,
Bartomeu Massuti,
Maria Sanchez-Ronco,
Rafael Rosell
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ABSTRACT: To assess the activity of induction chemotherapy followed by surgery in stage IIIA and selected stage IIIB non-small-cell lung cancer patients.
Mediastinoscopy proof of either positive N2 (IIIA) or T4N0-1 (IIIB) disease was required. Induction therapy was three cycles of cisplatin/gemcitabine/docetaxel, followed by surgery.
From December 1999 to March 2003, 136 patients were entered onto the study; the clinical response rate in 129 assessable patients was 56%. The overall complete resection rate was 68.9% of patients eligible for surgery (72% of stage IIIA patients and 66% of stage IIIB patients) and 48% of all assessable patients. Eight (12.9%) of 62 completely resected patients had a pathologic complete response. Seven patients (7.8%) died during the postoperative period. The median overall survival time was 15.9 months, 3-year survival rate was 36.8%, and 5-year survival rate was 21.1%, with no significant differences in survival between stage IIIA and stage IIIB patients. Median survival time was 48.5 months for 62 completely resected patients, 12.9 months for 13 incompletely resected patients, and 16.8 months for 15 nonresected patients (P = .005). Three- and 5-year survival rates were 60.1% and 41.4% for completely resected patients, 23.1% and 11.5% for incompletely resected patients, and 31.1% and 0% for nonresected patients, respectively. In the multivariate analysis, complete resection (hazard ratio [HR] = 0.35; P < .0001), clinical response (HR = 0.32; P < .0001), and age younger than 60 years (HR = 0.64; P = .027) were the most powerful prognostic factors.
Induction chemotherapy followed by surgery is effective in stage IIIA and in selected stage IIIB patients attaining complete resection.
Journal of Clinical Oncology 11/2007; 25(30):4736-42. · 18.37 Impact Factor
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ABSTRACT: Malignant melanoma is the most rapidly increasing cancer in the world. Metastatic disease occurs in 20% of patients, and prognosis in these cases is poor. We report the case of a woman who presented breast metastasis as the first sign of recurrence of a melanoma.
Clinical and Translational Oncology 02/2006; 8(1):57-9. · 1.33 Impact Factor
