Early palliative care and quality of life of advanced cancer patients-a multicenter randomized clinical trial.

BACKGROUND: To compare quality of life (QoL) of patients receiving early palliative care (EPC) vs. standard oncologic care (SOC). METHODS: Pragmatic, multicenter, randomized trial at five University and Community Hospital Cancer Centers in Northern Italy. Advanced non-small cell lung, gastric, pancreatic and biliary tract cancer patients diagnosed within the previous 8 weeks. In the EPC arm, visits were performed systematically by a dedicated physician/nurse palliative care (PC) team, who assessed physical and psychosocial symptoms, and enacted the necessary services. In the SOC arm, PC visits were only carried out if requested. The primary outcome was the difference in the change of QoL [Functional Assessment of Cancer Therapy-General measure (FACT-G)] from baseline to 12 weeks in the two groups. RESULTS: From November 2014 to March 2016, 281 patients were enrolled (142 EPC, 139 SOC); 218 completed FACT-G at 12 weeks. Baseline demographic and clinical characteristics were similar for the two groups. Values of FACT-G at baseline and 12 weeks were 72.3 (SD 12.6) and 70.1 (SD 15.5) for patients enrolled in the EPC arm, vs. 71.7 (SD 14.7) and 69.6 (SD 15.5) for the SOC arm, but the change scores did not differ significantly between groups. In the multivariable analysis, adjusting for QoL at baseline, two potential prospective prognostic factors were statistically significant: lung cancer (P=0.03) and interaction of living without a partner and intervention arm (P=0.01). Dying within 6 months (P<0.001) was also statistically significant. CONCLUSIONS: In this study, EPC did not improve QoL in advanced cancer patients, but our findings highlight aspects which may guide future research on EPC.

Position paper of the Italian Association of Medical Oncology on early palliative care in oncology practice (Simultaneous Care).

One of the priorities of personalized medicine regards the role of early integration of palliative care with cancer-directed treatments, called simultaneous care. This article, written by the Italian Association of Medical Oncology (AIOM) Simultaneous and Continuous Care Task Force, represents the position of Italian medical oncologists about simultaneous care, and is the result of a 2-step project: a Web-based survey among medical oncologists and a consensus conference. We present the opinion of more than 600 oncologists who helped formulate these recommendations. This document covers 4 main aspects of simultaneous care: 1) ethical, cultural, and relational aspects of cancer and implications for patient communication; 2) training of medical oncologists in palliative medicine; 3) research on the integration between cancer treatments and palliative care; and 4) organizational and management models for the realization of simultaneous care. The resulting recommendations highlight the role of skills and competence in palliative care along with implementation of adequate organizational models to accomplish simultaneous care, which is considered a high priority of AIOM in order to grant the best quality of life for cancer patients and their families.

Early Integration of Palliative Care in Oncology Practice: Results of the Italian Association of Medical Oncology (AIOM) Survey.

BACKGROUND: Early integration of palliative care in oncology practice ("simultaneous care", SC) has been shown to provide better care resulting in improved quality-of-life and also survival. We evaluated the opinions of Italian Association of Medical Oncology (AIOM) members. PATIENTS AND METHODS: A 37-item questionnaire was delivered to 1119 AIOM members. Main areas covered were: social, ethical, relational aspects of disease and communication, training, research, organizational and management models in SC. Three open questions explored the definition of Quality of Life, Medical Oncologist and Palliative Care. RESULTS: Four hundred and forty-nine (40.1%) medical oncologists returned the questionnaires. Forty-nine percent stated they address non-curability when giving a diagnosis of metastatic tumor, and 43% give the information only to patients who clearly ask for it. Fifty-five percent say the main formative activity in palliative medicine came from attending meetings and 90% agree that specific palliative care training should be part of the core curriculum in oncology. Twenty-two percent stated they consulted guidelines for symptom management, 45% relied upon personal experience and 26% make a referral to a palliative care specialist. Seventy-four percent were in favor of more research in palliative medicine. An integration between Units of Oncology and Palliative Care Services early in the course of advanced disease was advocated by 86%. Diverse and multifaceted definitions were given for the concepts of Quality of Life, Palliative Care and Medical Oncologist. CONCLUSION: SC is felt as an important task, as well as training of medical oncologists in symptom management and research in this field.

Activity and safety of dose-adjusted infusional cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy with rituximab in very elderly patients with poor-prognostic untreated diffuse large B-cell non-Hodgkin lymphoma.

BACKGROUND: This study was designed to assess the activity and safety of dose-adjusted infusional cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy with rituximab (DA-POCH-R) in elderly patients with poor-prognostic untreated diffuse large B-cell non-Hodgkin lymphoma (DLBCL). METHODS: From April 2006 to November 2009, 23 patients, aged ≥70 years, with an age-adjusted International Prognostic Index (IPI) of 2 or 3, were enrolled. Only patients with left ventricular ejection fraction (LVEF) ≥50% were allowed. The DA-POCH-R regimen was administered every 3 weeks for a minimum of 6 and a maximum of 8 cycles. RESULTS: Median patient age was 77 years (range, 70-90 years); 83% of patients had Ann Arbor stage III to IV disease. Median LVEF at baseline was 62%. Four (17%) patients had a history of abnormal cardiovascular conditions. Twenty-one (91%) patients were evaluable for response. The overall response rate was 90%, with a complete response rate of 57%. The 3-year overall survival and event-free survival rates were 56% and 54%, respectively. Neutropenia (48%) was the most frequent grade 3 to 4 adverse event (AE); no grade 3 to 4 cardiac AEs were observed. CONCLUSIONS: DA-POCH-R was an active and safe combination therapy for patients aged ≥70 years with poor-prognostic untreated DLBCL. This regimen was a reasonable alternative for elderly patients who were not considered to tolerate standard R-CHOP treatment.

Predictors of gefitinib outcomes in advanced non-small cell lung cancer (NSCLC): study of a comprehensive panel of molecular markers.

A number of different clinical characteristics and molecular markers related to epidermal growth factor receptor (EGFR) activation have been reported to singly correlate with therapeutic activity of EGFR tyrosine kinase inhibitors (TKIs) in advanced non-small cell lung cancer (NSCLC). This study was designed to evaluate the predictive value on gefitinib outcomes of a comprehensive panel of molecular parameters in advanced NSCLC patients. EGFR and K-ras mutations were detected by direct sequencing on tumor DNA from paraffin embedded samples. EGFR and HER2 gene copy number was assessed by FISH. EGFR protein expression was quantified by immunohistochemistry. EGFR gene intron 1 polymorphism was assessed on genomic DNA isolated from venous whole blood samples. Ninety-one patients were prospectively enrolled and the overall gefitinib response rate was 18.7% (2 complete and 15 partial responses). Sex (p=0.005), non-smoking status (p=0.010), skin toxicity (p=0.020), EGFR gene mutations (p<0.001) and EGFR FISH positivity (p=0.016) were found to be associated with gefitinib response. K-ras mutation was detected in only seven non-responder patients. The median overall survival was of 10 months. Only non-smoking status and EGFR intron 1 polymorphism showed a statistically significant correlation with survival (p=0.031 and 0.044, respectively). In conclusion, we have confirmed the role of EGFR gene mutation as predictor of response to EGFR TKIs. Moreover, EGFR gene copy number and, potentially, also EGFR intron 1 polymorphism could aid in better prediction of EGFR TKI responsiveness in advanced NSCLC.

Epidermal growth factor receptor intron-1 polymorphism predicts gefitinib outcome in advanced non-small cell lung cancer.

INTRODUCTION: Epidermal growth factor receptor (EGFR) gene intron 1 contains a polymorphic single sequence dinucleotide repeat (CA)n whose length has been found to inversely correlate with transcriptional activity. This study was designed to assess the role of (CA)n polymorphism in predicting the outcome of gefitinib treatment in advanced non-small cell lung cancer (NSCLC). METHODS: Blood and tumor tissue from 58 patients with advanced NSCLC submitted to gefitinib were collected. EGFR intron 1 gene polymorphism, along with EGFR gene mutation, gene copy number and immunohistochemistry expression were determined. Moreover, a panel of lung cancer cell lines characterized for EGFR intron 1 polymorphism was also studied. RESULTS: EGFR intron 1 polymorphism showed a statistically significant correlation with the gefitinib response (response rate 25 versus 0%, for patients with a (CA)16 and with a (CA)else genotype, respectively; p = 0.044). Patients with a (CA)16 genotype had a longer survival compared with those with a (CA)else genotype (11.4 versus 4.8 months, respectively; p = 0.037). In addition, cell lines lacking the (CA)16 allele showed a statistically significant higher IC50 compared with cell lines bearing at least one (CA)16 allele (p = 0.003). CONCLUSIONS: This study supports a potential role of EGFR intron 1 polymorphism in predicting the outcome of gefitinib treatment in advanced NSCLC.

Comparison between epidermal growth factor receptor (EGFR) gene expression in primary non-small cell lung cancer (NSCLC) and in fine-needle aspirates from distant metastatic sites.

PURPOSE: Epidermal growth factor receptor (EGFR) gene copy number obtained by fluorescence in situ hybridization (FISH) has been recently found to predict treatment outcome in non-small cell lung cancer (NSCLC) patients receiving EGFR tyrosine kinase inhibitors. However, it is still unknown whether EGFR status differs in metastases compared with primary NSCLC. In all studies FISH have been performed on histologic material. The possibility to perform FISH analysis on cytologic material obtained by fine-needle aspiration from superficial and visceral metastases would allow us to know the real EGFR status avoiding invasive diagnostic procedures. METHODS: EGFR gene copy number was analyzed by FISH on fine-needle aspirates obtained from 31 patients with metastatic NSCLC and the results were compared with those obtained on corresponding paraffin histologic sections from the primary tumor. RESULTS: The feasibility of EGFR FISH on cytology was 90% (28 of 31 patients). EGFR FISH was positive in 61% (17 of 28 patients) of the metastases and in 36% (10 of 28 patients) of the primary tumors. Nine of the 28 cases (32%) were EGFR positive on both primary tumor and metastatic site and 10 (36%) were negative on both primary tumor and metastasis. Nine of the 28 cases (32%) showed discordance of primary tumor versus metastasis (McNemar test; p = 0.041). CONCLUSIONS: EGFR FISH can be reliably assessed on fine-needle aspirates obtained from NSCLC metastases. We found that EGFR gene copy number is discordant between primary NSCLC and the corresponding distant metastatic sites in a significant proportion of cases. These findings should be considered in future studies designed to elucidate the predictive role of EGFR FISH in NSCLC.

Buccal mucosa cells as in vivo model to evaluate gefitinib activity in patients with advanced non small cell lung cancer.

PURPOSE: To evaluate the role of pretreatment and posttreatment expression in buccal mucosa cells of signal transduction proteins activated by epidermal growth factor receptor, including phosphorylated epidermal growth factor receptor (p-EGFR), phosphorylated mitogen-activated protein kinase (p-MAPK), and phosphorylated AKT (p-AKT), in predicting gefitinib activity in advanced non-small cell lung cancer patients. Expression of the same proteins was also assessed on corresponding tissue samples for comparison. Moreover, EGFR gene mutations and copy number were analyzed. EXPERIMENTAL DESIGN: Protein expression was evaluated by standard immunocytochemistry in buccal smears, obtained by scraping immediately before and after 2 weeks of gefitinib treatment, and in the available archival tumor specimens. EGFR gene mutations were evaluated by direct sequencing and gene copy number was determined by fluorescence in situ hybridization. Data were correlated with gefitinib toxicity and objective response. RESULTS: Fifty-eight patients with pretreated advanced non-small cell lung cancer were enrolled and nine of these patients (15%) showed an objective response to gefitinib (including two complete responses). Toxicity (P = 0.025) and baseline p-AKT expression in buccal mucosa cells (P = 0.061) showed a potential predictive role. On the contrary, the probability of achieving an objective response was not affected by pretreatment expression of EGFR, p-EGFR, and p-MAPK, either in buccal mucosa or in tumor tissue. Responders showed a nonstatistically significant trend toward a more pronounced reduction in the expression of p-EGFR, p-MAPK, and p-AKT after gefitinib treatment. Among responders, five of six (83%) tumors showed EGFR gene mutation, whereas none of the tumors from patients with stable or progressive disease did (P < 0.001). CONCLUSIONS: Epithelial cells obtained from buccal mucosa may be used to assess the pharmacodynamic effect of EGFR-targeted agents, and pretreatment p-AKT expression may be a possible predictive biomarker of in vivo gefitinib activity.

Tamoxifen vs Tamoxifen plus 13-cis-retinoic acid vs Tamoxifen plus Interferon alpha-2a as first-line endocrine treatments in advanced breast cancer: updated results of a phase II, prospective, randomised multicentre trial.

AIMS AND BACKGROUND: To demonstrate the efficacy of 13-cis-retinoic acid (RA) or Interferon alpha-2a (IFN alpha-2a) with Tamoxifen (TAM) in the treatment of advanced breast cancer. METHODS: Ninety-nine postmenopausal patients with advanced breast cancer, and a positive or unknown estrogen (ER) or progesterone (PgR) receptor status, were randomised to receive TAM 20 mg/m2/day orally (arm A), or TAM plus RA 1 mg/kg/day orally (arm B), or TAM plus IFN alpha-2a 3 MU thrice a week intramuscular (arm C). The three treatment groups were well balanced in terms of the main prognostic factors. RESULTS: Response was evaluable in 32 of the patients in arm A, 32 in arm B, and 30 in arm C. Intention-to-treat analysis showed no significant difference of response rate in the three arms (44% vs 38% vs 42%). After an eight years median follow-up, there was no significant between-group difference in median overall survival: 47.4 vs 38.2 vs 45.1 months. Side effects were negligible in arm A, but cutaneous (39%) and mucosal (62%) toxicities were frequent in arm B, and flu-like syndrome and/or myalgia (46%) in arm C. CONCLUSIONS: The administration of RA or IFN alpha-2a does not add anything to the therapeutic effects of TAM.

Capecitabine and mitomycin C may be an effective treatment option for third-line chemotherapy in advanced colorectal cancer.

AIMS AND BACKGROUND: We evaluated the activity in terms of time to progression (TTP) of mitomycin C and capecitabine in patients with advanced colorectal cancer who progressed after 2 lines of chemotherapy. METHODS: Patients with advanced colorectal cancer undergoing third-line chemotherapy after failure of 5-FU with CPT-11 or oxaliplatin-based chemotherapy regimens were treated with capecitabine and mitomycin C. RESULTS: Sixty-one patients were enrolled in this study. The median age was 55 years (range, 26-78 years) and the male:female ratio 21:40. We observed partial remissions in 5 patients (8%), stable disease in 25 patients (40%) and progression of disease in 31 patients (52%). Median TTP was 3 months and median survival was 6 months. Global toxicity was mild and entirely acceptable. Grade 3-4 hematological toxicity occurred in 12 patients and grade 3-4 nonhematological toxicity in 5 patients. CONCLUSIONS: The combination of capecitabine and mitomycin C could represent an effective and manageable treatment option for colorectal cancer patients failing previous chemotherapy regimens.

Mismatch repair system (MMR) status correlates with response and survival in non-small cell lung cancer (NSCLC) patients.

Pre-clinical data suggested a relationship between inactivation of hMLH1 and hMSH2 and resistance to drugs like cisplatin and carboplatin, but not oxaliplatin. We then hypothesised that NSCLC showing loss of expression of the mismatch repair system (MMR), could be refractory to cisplatin-based, but not to oxaliplatin-based chemotherapy. Immunohistochemical expression of hMLH1 and hMSH2 was analysed on tumour samples from 93 advanced NSCLC, receiving chemotherapy with either cisplatin or oxaliplatin in combination with gemcitabine. Patients showing loss of hMLH1 or hMSH2 expression in > or = 50% of tumour cells were deemed MMR-negative (Group A), whereas cases with a normal hMLH1 or hMSH2 expression in > 50% of the tumour cells were defined MMR-positive (Group B). No differences in the response and progression rate were found in the whole patients population and in the gemcitabine/cisplatin group for both hMLH1 and hMSH2. In the gemcitabine/oxaliplatin group response rate was 38% and 0% (p=0.04) for patients with or without loss of hMSH2 expression. Median survival according to MMR status in Groups A and B, respectively was: 17 months versus 9 months for hMLH1 (p=0.031) and 10 months versus 9 months for hMSH2 (p=0.8330). Both the difference in response rate and in median survival observed according to MMR status seem to confirm what has been suggested by preclinical studies.

Lomustine (chloroethylnitrosourea [CCNU]), ifosfamide, bleomycin, vincristine, and cisplatin (CIBO-P) is an effective regimen for patients with poor prognostic refractory or multiple disease recurrent aggressive non-Hodgkin lymphoma.

BACKGROUND: The current study was designed to assess the activity and safety of a novel combination therapy for patients with recurrent or refractory aggressive non-Hodgkin lymphoma (NHL). METHODS: Forty-three consecutive patients with recurrent or refractory aggressive NHL were treated with lomustine (chloroethylnitrosourea [CCNU]; 60 mg/m2 on Day 1), ifosfamide (1.5 g/m(2 on Days 1, 2 and 21, 22), bleomycin (5 mg/m2 on Days 1, 5 and 21, 25), vincristine (1.4 mg/m2 on Days 1, 8 and 21, 28), and cisplatin (25 mg/m2 on Days 3, 4, 5 and 23, 24, 25), every 42 days (CIBO-P regimen). RESULTS: Thirty-nine patients (91%) were evaluable for response. The median patient age was 63 years. Thirty-five percent of the patients had received > or = 2 lines of previous chemotherapy and 40% had elevated lactate dehydrogenase levels at the time of treatment initiation. The overall objective response rate was 77% (95% confidence interval [95% CI], 63-90%), including 19 (49%) complete (CR) and 11 (28%) partial responses. CIBO-P induced responses in primary refractory disease and in patients treated for second or subsequent disease recurrences. A CR with previous therapy was the most important factor associated with a significantly higher CR rate. The median duration of response was 6 months (95% CI, 4.4-7.7 months) and the median survival duration was 10.7 months (95% CI, 5.9-18.1 months). Five patients (11.6%) remained disease free for > or = 24 months. By multivariate analysis, a CR with previous therapy and average dose intensity of CIBO-P drugs were independent prognostic factors for time-to-treatment failure, whereas a CR with previous therapy and serum lactate dehydrogenase were independent predictors for survival. Myelosuppression was the most frequent serious complication of this regimen. However, none of the patients had hemorrhage with thrombocytopenia, and only 2 patients (5%) had febrile neutropenia. CONCLUSIONS: In the current study, CIBO-P was a novel, highly active, and safe combination therapy for patients with refractory disease with a poor prognosis or for patients with multiply recurrent aggressive NHL.

Molecular profile and clinical variables in BRCA1-positive breast cancers. A population-based study.

PURPOSE: To evaluate the clinical features of breast cancer patients with genetic susceptibility to this disease and to investigate the contribution of BRCA1 germline mutations to the phenotype of these tumors. PATIENTS AND METHODS: We reviewed the clinical and pathological records of 102 women with suspected inherited susceptibility to breast cancer consecutively seen at the Genetic Oncology Service of Parma, Italy. Sixty-two patients with a high probability of harboring a germline, cancer-predisposing mutation were tested for BRCA1 mutations. Exon 11 was screened using the protein truncation test and detected mutations were confirmed by direct sequencing (DS). All other exons were analyzed by DS. RESULTS: Among the 62 patients with a completed mutation analysis, 48 (77.4%) had wild-type BRCA1, six (9.6%) had variants of unclear significance, eight (13%) had deleterious mutations. BRCA1-associated breast cancers (BABC) were significantly less likely to be diagnosed at stage I than breast cancers in women without mutations (12.5% vs 51%; P = 0.045), more likely to have a high proliferation rate (100% vs 24%, P < 0.001), and more likely to be histological grade 3 (100% vs 14%, P < 0.001), estrogen and progesterone receptor negative (87.5% vs 13%, P < 0.001; 75% vs 23%, P = 0.004), and p53 positive (87.5% vs 30%, P = 0.023). All tumors with BRCA1 mutations were HER-2/neu negative compared with 57% of the non-BRCA1 tumors (P = 0.04). There were no significant differences between BABC and non-BABC in 20-year relapse-free survival, 20-year event-free survival, and 20-year overall survival. CONCLUSION: In this population-based study, BABC seems to present with adverse molecular features when compared with non-BABC, although the prognosis appears to be similar.

Early detection of recurrences in the follow-up of primary breast cancer in an asymptomatic or symptomatic phase.

AIMS AND BACKGROUND: Periodic follow-up after primary treatment for breast cancer is a common procedure for the early detection of recurrent disease in the asymptomatic state. Anyway, there is no clinical evidence that treatment of metastases may improve the prognosis if applied in the asymptomatic state. The aim of the present study was to investigate the modality of detection of the first relapse in the asymptomatic vs the symptomatic state. METHODS: We retrospectively analyzed 717 breast cancer patients who had been consecutively referred to the Parma Oncology Division during the period 1986 to December 1988. Recurrences were detected in the course of periodic follow-up. RESULTS: A total of 211 of the 408 patients evaluated had a first relapse with a median follow-up of 94.7 months. Local and distant recurrences were 49% and 47%, respectively. Bone recurrences represented 24% of the total first recurrences, then chest wall recurrences in 23%, local regional nodes in 13%, lung in 7%, liver in 4%, and brain in 2%. The distribution of the studied patients according to recurrence site and asymptomatic or symptomatic state was different: 69% of asymptomatic patients (110) had a local recurrence vs 31% of symptomatic patients (101). A difference in survival was recorded in favor of cases detected in the asymptomatic state (P <0.001). CONCLUSIONS: The present study suggests that an early detection of local recurrence might have a favorable impact on the prognosis of patients followed after primary treatment for breast cancer. It should be considered that any difference in survival could also be explained by several "biases" and that breast cancer follow-up is still an area of investigation open to discussion in which many questions remain to be clarified.

P-CHOP: cisplatin (P) added to the standard CHOP regimen as first-line treatment for aggressive non-Hodgkin lymphoma: a single-institution phase II study.

We designed the P-CHOP regimen, which involves the addition of cisplatin (P) to the standard CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) regimen, and investigated its activity and its toxicities in a single institution phase II study. Twenty-two consecutive patients with untreated, aggressive, stage I-IV non-Hodgkin lymphoma were enrolled in the study. Cisplatin was administered at a dose of 40 mg/m2 on days 1 and 2, every 3 weeks; the dose and schedule of the other agents were identical to those used in the standard CHOP regimen. The complete remission (CR) rate was 86% in eligible and 80% in all the treated patients, which compares favorably with the CR rates of two recent randomized studies of CHOP versus other regimens. P-CHOP is an innovative regimen for the front-line treatment of aggressive non-Hodgkin lymphoma. It is feasible and warrants further research, which would ideally take the form of a randomized comparison of P-CHOP and CHOP, possibly with the addition of rituximab in both arms.

HER-2/neu amplification by fluorescence in situ hybridization in cytologic samples from distant metastatic sites of breast carcinoma.

BACKGROUND: Amplification of the HER-2/neu oncogene has been proposed as a target for antibody-based therapies and as a predictor of chemoresponsiveness in advanced breast carcinoma. Few studies have concentrated on HER-2/neu gene evaluation by fluorescence in situ hybridization (FISH) on distant metastatic sites and none have been performed on cytologic samples. The current study evaluated HER-2/neu amplification by FISH on cytologic samples obtained from distant metastatic lesions of breast carcinoma to update HER-2/neu characterization through a safe and easier procedure than biopsy. METHODS: Twenty-two cytologic samples from distant metastases (12 hepatic samples, 4 skin samples, 3 pleural samples, and 3 peritoneal samples) were submitted to HER-2/neu evaluation by FISH. Seventeen corresponding primary breast tumors also were evaluated by FISH on paraffin histologic sections or on destained archival cytologic smears. RESULTS: Seven of the 22 metastases (32%) were amplified. Amplification was observed in 4 of the 12 liver metastases, in 1of the 3 ascitic fluid specimens, and in 2 of the 4 skin metastases. In all the three pleural fluid specimens, HER-2/neu was unamplified. Matched results from primary and metastatic lesions were obtained in 14 cases (5 were amplified and 9 were unamplified on both primary and metastatic tumors). CONCLUSIONS: The results of the current study emphasized the feasibility and advantages of two rapid and very informative techniques, such as fine-needle aspiration biopsy and FISH. Both procedures were performed to ascertain the malignant nature of a suspicious lesion and to obtain predictive markers for response. Since the advent of trastuzumab, the characterization of the molecular profile in metastatic breast disease has become increasingly important for targeted therapy selection.

Gemcitabine and oxaliplatin: a safe and active regimen in poor prognosis advanced non-small cell lung cancer patients.

BACKGROUND AND AIMS: Most patients with non-small cell lung cancer (NSCLC) cannot tolerate a cisplatin-based chemotherapy because of old age, general conditions, and/or multiorgan metastatic sites. Oxaliplatin is active in NSCLC, offers advantage in terms of toxicity, and shows synergism with gemcitabine. The aims of this phase II study were to evaluate the response rate and toxicity of the gemcitabine-oxaliplatin combination in patients with advanced NSCLC and poor prognosis. METHODS: Patients were given a gemcitabine infusion (1000 mg/m(2) over 30 min on days 1 and 8) followed by oxaliplatin (65 mg/m(2) over 120 min on days 1 and 8) every 21 days for six cycles. RESULTS: Thirty-two patients with poor-prognosis advanced NSCLC received 136 cycles. There were 25 males and seven females, and the median age was 65 years (range 29-76). Fifty-six percent of patients had adenocarcinoma, and 31% had squamous cell carcinoma. Sixty-six percent of patients had stage IV disease, and 34% had stage IIIB disease. Eastern cooperative oncology group (ECOG) performance status was 2-3 in 50%, 1 in 44%, and 0 in 6% of patients. Eight patients (25%) had been previously treated with cisplatin or carboplatin. All patients were symptomatic. Of the 32 patients who received study drug, five (16%) achieved partial response, six (19%) had minor response, three (9%) had stable disease, and 15 (47%) progressed. The median overall survival was 27 weeks. Thirty-one patients were evaluable for toxicity: seven patients (23%) had grade 3-4 thrombocytopenia with no bleeding; four patients (13%) had grade 3-4 neutropenia with no febrile neutropenia, and three patients (10%) had grade 3 anemia. Two patients (6%) had grade 3, and six patients (19%) had grade 1-2 neurotoxicity. CONCLUSION: The combination of gemcitabine and oxaliplatin seems to be well tolerated and active in patients with poor prognosis advanced NSCLC and deserves further evaluation in phase II clinical trials.

Compliance and outcomes in locally advanced head and neck cancer patients treated with alternating chemo-radiotherapy in clinical practice.

BACKGROUND AND AIMS: To evaluate the feasibility in clinical practice of alternating chemo-radiotherapy in locally advanced head and neck cancer patients. PATIENTS AND METHODS: From August 1993 to April 1998 at the Division of Medical Oncology of Parma, 48 consecutive patients were observed, and 38 (79%) started the Merlano chemo-radiotherapy. The characteristics of the patients were: males (32, 84%); median age, 57 years; PS <2 (32, 84%). The primary sites were the oropharynx (18, 47%), oral cavity (8, 21%), hypopharynx (7, 19%), larynx (5, 13%); stage IV disease was present in 29 (76%) patients. Twenty-five (66%) patients were married, and 24 (63%) resided outside of the city. RESULTS: The compliance was very low: 21 patients (55%) performed all the programmed cycles of chemotherapy, whereas only 5 patients (13%) performed the chemo-radiotherapy at full doses without any delay. The objective responses were 3 (8%) complete and 21 (55%) complete plus partial responses. Failures were 2 (5%) stable disease and 2 (5%) progressive disease, and the response was not assessable in 10 (26%). The median duration of the response was 8 months. The median overall survival and the time to progression were 18 and 13 months, respectively; the 5-year overall and relapse-free survival were 36% and 26%, respectively. Nine (24%) patients were still alive as of August 30, 2001, 8 (21%) of them without progression. Twenty-six patients (68%) died with a local-regional relapse. One patient (3%) died for a second cancer. Grade 3-4 hematologic toxicity was leukopenia (n = 25, 66%) and thrombocytopenia (n = 9, 24%); grade 3-4 non-hematologic toxicity was diarrhea (n = 3, 8%) and mucositis (n = 2, 5%). Two patients (5%) died for intestinal infarction and perforation possibly related to treatment. CONCLUSIONS: Compliance to the chemo-radiotherapy was very poor. The response rate was lower than that reported in clinical trials, whereas overall survival was comparable. The alternating chemo-radiotherapy is a very complex treatment that cannot be easily applied in clinical practice; a careful selection of patients is mandatory not only considering oncologic and medical criteria, but also the level of awareness of the patient and his family.