Domenico Gattuso

Pain and its treatment in hospitalized patients with metastatic cancer

GoalsThe aim of this prospective study was to assess the quality of pain management hospitalized cancer patients.Patients and methodsIn a quantitative and qualitative evaluation from six oncology centers in Italy, all consecutive cancer patients complaining of pain and hospitalized during the same 2 weeks were requested to fill in a McGill pain questionnaire (MPQ), a present pain intensity scale (PPI), and a hospital anxiety and depression acale (HADS), and to answer a questionnaire focused (QF) on the quality of medical and nursing care. The healthcare providers antalgic prescriptions were assessed by an index of pain management (IPM).Main resultsOf 120 patients with pain admitted to oncology divisions (65 men and 52 women; mean age 57 years, range 21–79 years), 117 completed the questionnaires. The quantitative evaluation (PPI) showed a significant pain reduction between admission and discharge pain levels—from 2.65 to 1.50 (p<0.001). While a significant reduction of anxiety (HADS) was also found—from 10.24 to 9.11 (p<0.001)—depression did not improve (9.83 and 9.72). The most relevant information from qualitative evaluation (QF) was: in 37.6% of patients, pain level was higher overnight; 47% waited for spontaneous decrease of pain intensity before asking for nurse or physician intervention; 69% asked for nurse help when pain level was really high. The health care response to patients pain was not completely satisfactory, since analgesic prescription was adequate in 56.52% but inadequate in 43.47%.ConclusionsPain control in hospitalized cancer patients is not completely satisfactory. The physicians attitude is to underestimate and undertreat pain, while nurses are not adequately trained for timely intervention despite published guidelines for pain management. The findings of this study support the concern of inadequate knowledge and inappropriate attitudes regarding pain management, even in cancer patients hospitalized in medical oncology divisions.

The combination of the selective cyclooxygenase-2 inhibitor celecoxib with weekly paclitaxel is a safe and active second-line therapy for non-small cell lung cancer: a phase II study with biological correlates.

PURPOSEThe selection of effective schedules of treatment for metastatic non-small cell lung cancer still remains a challenge for the oncologist. The present multicentric phase II study was designed in order to investigate the activity and safety of the combination of weekly paclitaxel and celecoxib as second-line treatment for non-small cell lung cancer. As a secondary endpoint, the possible correlation of biomarkers with objective response was investigated in a subset of patients. PATIENTS AND METHODSPatients with platinum-refractory non-small cell lung cancer and Eastern Cooperative Oncology Group performance status 0–2 entered the present phase II study. Paclitaxel was administered at the dose of 80 mg/m2 i.v. weekly for 6 weeks, followed by a 2-week rest, and celecoxib, 400 mg p.o. b.i.d. administered continuously. A cycle consisted of 8 weeks of treatment. Determination of circulating vascular endothelial growth factor and interleukin 6 was performed at baseline and every two cycles. RESULTSFifty-eight patients were enrolled: median age, 60 years (range, 30–77 years); male/female ratio = 44/14; performance status, 0, 31 patients; 1, 25 patients; and 2, two patients. Predominant histotype was adenocarcinoma (34 cases), and most patients had at least two sites of disease. According to the intent-to-treat analysis, 14/58 objective responses (24.1%) and 24/58 (41.3%) stabilizations of disease were observed, with a median duration of 4 months (range, 2–22+ months) and 5 months (range, 1–13 months), respectively. Median time to progression and median overall survival were 5 and 11 months, respectively. One-year survival was 42.5%. The main toxicity was neuropathy (4% of grade 3). Preliminary results suggest that decrease in serum vascular endothelial growth factor level is significantly associated with clinical response. DISCUSSIONCombination of celecoxib and weekly paclitaxel is a safe and active new regimen in pretreated non-small cell lung cancer. Toxicity appears not to be worsened by the addition of celecoxib. According to preliminary results, serum vascular endothelial growth factor level seems to be predictive of response, suggesting that it should be further investigated as a surrogate marker of response.

Thalidomide: a new anticancer drug?

Experimental studies have demonstrated that thalidomide (Thal), a drug developed as a sedative, has antitumoural properties. The possible antitumour mechanisms of action involve: inhibition of angiogenesis, cytokine-mediated pathways, modulation of adhesion molecules, inhibition of cyclooxygenase-2 and stimulation of immuno response. Therefore, Thal is under clinical evaluation in oncology. This paper provides an overview of the data currently available in literature regarding, in terms of activity and toxicity, the use of Thal in cancer patients. Multiple myeloma is so far the most responsive malignancy. A moderate activity has been documented in certain solid tumours: glioblastoma multiforme, renal cell carcinoma and malignant melanoma. Tolerability is generally satisfactory with peripheral neuropathy being the most relevant dose-dependent toxicity. The more frequent, but moderate side effects are: somnolence, constipation, dizziness and fatigue. More studies are needed to properly evaluate the anticancer activity of Thal alone or in combination with other anticancer treatments. Preliminary studies suggest promising results of Thal in combinations with corticosteroids and cytotoxic drugs as front-line therapy of multiple myeloma. Regarding therapy of solid tumours in the adult, combination with chemotherapy, radiation therapy and molecular-targeting compounds are under investigation.

The combination of gemcitabine and vinorelbine is an active regimen as second-line therapy in patients with metastatic breast cancer pretreated with taxanes and/or anthracyclines: a phase I-II study.

AbstractPurpose. To evaluate the activity and toxicity of gemcitabine and vinorelbine (GemVin), in patients with advanced breast cancer, previously treated with anthracyclines alone or with taxanes.nPatients and methods. Nine patients were entered into the phase I and 50 patients were entered into the phase II study. Gemcitabine was administered beginning with the dose of 800 mg/m2 and vinorelbine was given at the fixed dose of 25 mg/m2, both on days 1 and 8, every 21 days. Escalated dose levels of gemcitabine were planned by increments of 200 mg/m2 per level. The median age of the 50 assessable patients for the phase II study was 56.5 years (range 30–70) and median performance status (PS, ECOG score), 1 (range 0–2). The dominant sites of metastases were viscera in 40, bone in five and soft tissue in five patients. First-line chemotherapy for metastatic disease with taxanes and anthracyclines or with anthracyclines alone was administered in 36 and 14 patients, respectively.nResults. The optimal schedule for the combination was gemcitabine 800 mg/m2 and vinorelbine 25 mg/m2. The maximum tolerated dose of gemcitabine was 1000 mg/m2, with grade 4 neutropenia occurring in two cases at this dose level. Overall, 267 cycles were given to the 50 patients enrolled into the phase II (mean 5.3; range 3–9). The schedule was well tolerated: three patients experienced grade 4 neutropenia and another four patients experienced grade 3 anemia. Non-hematological toxicities were moderate. A major objective response was observed in 42% of patients (95% confidence interval (CI), 28–57%), with complete remission in four (8%) and partial response in 17 (34%) patients. The median time to progression was 6 months. Activity as well as toxicity were similar in the subgroups of the patients pretreated either with combinations of taxanes and anthracyclines or anthracyclines alone.nConclusions. The optimal GemVin schedule is an effective and well tolerated second-line therapy in patients with metastatic breast cancer pre-treated with anthracycline – based schedules or with combinations of anthracyclines and taxanes.

Clinical management of a case of recurrent apocrine gland carcinoma of the scalp: Efficacy of a chemotherapy schedule with methotrexate and bleomycin

Apocrine carcinoma of the skin is a rare tumor. Wide surgical excision with complete removal of the neoplasm is the standard therapy and this appears to offer the best chance of cure. Radiotherapy may be used in case of local relapse or regional lymph node involvement. Systemic chemotherapy has not proved to be effective in the treatment of this tumor. We report on a 46-year-old woman with a recurrent apocrine carcinoma of the scalp that had previously been treated with surgery, radiotherapy and chemotherapy (Al-Saraff schedule). The patient was responsive to a second-line systemic chemotherapy regimen consisting of a weekly combination of methotrexate and bleomycin, and achieved long-term progression-free survival.

Safety and activity of the combination of pegylated liposomal doxorubicin and weekly docetaxel in advanced breast cancer.

Background. The present study was designed with the aim of evaluating the tolerability and activity of pegylated liposomial doxorubicin (PLD) in combination with weekly docetaxel as first line treatment of advanced breast cancer. Patients and methods. Fifty-seven patients entered the study. PLD was administered at escalating doses starting from 30 mg/m, on day 1; docetaxel was administered at the fixed dose of 35 mg/m on days 2 and 9. A cycle of therapy consisted of 21 days. Results. The MTD was achieved at the dose of 40 mg/m of PLD, being febrile neutropenia and palmar-plantar-erythrodisesthesia (PPE) the dose-limiting toxicities (DLTs), so that the fixed dose of PLD for the Phase II study was 35 mg/m. Forty-two consecutive patients received treatment at the established dose for a total of 194 cycles: among these, three patients were withdrawn for severe allergic reaction at the first administration of PLD. Hematological toxicity was moderate, the most common grade 1–3 non-hematological toxicities were stomatitis and PPE, occurring in 20 (47.5%) and 16 (38%) patients, respectively. No cardiac toxicity was recorded. According to the intent to treat analysis a major objective response was observed in 59.5% of patients (95% CI, 43.3–74.4%), with a median time to progression of 9months and an estimated overall survival at 18 months of 62%. Conclusion. The combination of PLD and weekly docetaxel is an effective first-line therapy for patients with advanced breast cancer. PPE and mucositis are the most relevant side effects of such a combination.

Primary Nongestational Choriocarcinoma of the Uterine Cervix

In December 2009, a 54-year-old postmenopausal Indian woman was admitted to our hospital for abdominal pain and severe vaginal hemorrhage. A pelvic and transvaginal ultrasound scan showed the presence of a cervical uterine mass. Blood analysis demonstrated a moderate anemia and elevated serum -human chorionic gonadotropin ( -HCG) levels (29,976.41 mU/mL; normal value, 5 mU/mL). The patient underwent radical hysterectomy in emergency with documentation of a large and highly hemorrhagic and friable tumor lesion occupying the whole cervical canal (Fig 1A, black arrows). Histology revealed the presence of a plexiform pattern with cytotrophoblastic and syncytiotrophoblastic cells. The first component, centrally situated, was characterized by medium-sized cells, whereas the peripheral one was composed of large, multinucleated cells (Fig 1B, black arrows). Immunohistochemical staining of tumor cells was positive for -HCG (Fig 1C, red arrows), confirming the diagnosis of cervical choriocarcinoma. Postsurgical whole-body computed tomography scan documented the presence of multiple metastases in the liver, lungs, and abdominal lymph nodes. The patient was treated with systemic chemotherapy with a combination of cisplatin, etoposide, and bleomycin for four cycles, obtaining a complete radiologic response and normalization of serum -HCG. Two months later, a whole-body computed tomography scan showed a liver, lung, and lymph nodes disease progression associated with increased serum -HCG levels (254.56 mU/mL; normal value, 5 mU/mL). Therefore, we started a second-line chemotherapy with a combination of cisplatin, vinblastine, and ifosfamide. After two cycles of therapy, the patient underwent whole-brain radiotherapy for symptomatic brain metastases. She died a month later. In women, choriocarcinoma usually arises in the uterine cavity, and it is associated with coincident or previous pregnancy. Extrauterine choriocarcinoma is a rare entity, with the uterine cervix being the most common site and only a few cases reported in the literature to date. Several hypotheses have been postulated to explain the pathogenesis of cervical choriocarcinoma. It may develop from cervical metastases from a primary tumor in the corpus that later spontaneously regresses, malignant transformation of a cervical pregnancy, or transport of chorionic cells from a previous pregnancy that undergo malignant transformations after a dormant period. The accurate diagnosis is difficult because of its rarity. Furthermore, the majority of cases present with abnormal vaginal bleeding that could be caused by other more common conditions, including threatened abortion, cervical polyp, cervical pregnancy, or cervical cancer, leading to a potential misdiagnosis. Histology with immunohistochemical evaluation

Atypical Multiple Ileum Metastases of Renal Cell Carcinoma

Intestinal metastases of renal cell carcinoma (RCC) are very uncommon and only a few cases have been reported in the literature to date. The interval from diagnosis of the primary tumor to clinical presentation of small bowel metastases is variable and it seems to correlate with overall survival. Symptoms include abdominal pain, bleeding, perforation, and/or obstruction by an intussusception mechanism. The optimal treatment remains controversial and it depends on clinical patient’s conditions, comorbidities, and the pattern of tumor diffusion. The management should be aggressive since metastasectomy may extend patient survival. We report a rare case of a patient with a history of metachronous bilateral RCC and asymptomatic adrenal pheochromocytoma who developed, 1 year after a solitary metastasis in the proximal phalanx of the big toe, which was surgically removed, two metachronous ileum metastases. After a radical resection of these lesions, a standard second-line therapy with everolimus was started leading to a prolonged disease stabilization and survival. Case Report