Esthesioneuroblastoma (Olfactory Neuroblastoma) with Ectopic ACTH Syndrome: a multidisciplinary case presentation from the Joan Karnell cancer center of Pennsylvania Hospital.

The case of a patient with recurrent esthesioneuroblastoma complicated by ectopic adrenocorticotropic hormone production is presented, including the workup and management of this uncommon complication of an uncommon disease.

Single-arm, open label study of pemetrexed plus cisplatin in chemotherapy naïve patients with malignant pleural mesothelioma: outcomes of an expanded access program.

BACKGROUND: An expanded access program (EAP) provided patient access to pemetrexed prior to its commercial availability. The current report consists of US patients in the EAP who had chemotherapy naïve pleural mesothelioma. METHODS: Eligible patients had a histologic or cytologic diagnosis of malignant mesothelioma that was not amenable to curative treatment with surgery. Study treatment consisted of pemetrexed 500mg/m(2) in combination with cisplatin 75mg/m(2) once every 21 days. Vitamin B12, folic acid, and dexamethasone were administered as prophylaxis. Serious adverse events (SAEs) were reported by investigators and compiled in a pharmacovigilance database for all patients enrolled in the EAP. RESULTS: Of 1056 patients receiving at least one dose of pemetrexed in the EAP, 728 had chemotherapy naïve pleural mesothelioma. Median age of this group was 70 years (range 23-89 years) and 84% were male. Among 615 patients, overall response rate was 20.5%, including 12 complete responses (2.0%) and 114 partial responses (18.5%). An additional 290 patients (47.2%) had stable disease. Median survival for all 728 patients was 10.8 months (95% CI=9.8, 12.3; 60.3% censorship) and 1 year survival was 45.4%. The most commonly reported SAEs in the overall EAP irrespective of causality were dehydration (7.2%), nausea (5.2%), vomiting (4.9%), dyspnea (3.8%), and pulmonary embolism (2.4%). CONCLUSIONS: In this large cohort, 67.7% of patients treated with first-line chemotherapy experienced a response or stable disease. Survival time and toxicity from this EAP were promising for this difficult-to-treat disease.

Treating one of our own.

As a group, oncology nurses are aging, mirroring a large portion of the American public. Many practicing nurses are approaching middle age, and with increased age comes an increased risk for cancer. Many oncology nurses are cancer survivors, and the experience of treating a colleague is becoming more common, but few publications have addressed this topic. Pennsylvania Oncology Hematology Associates (POHA), a private medical oncology practice in Philadelphia, has encountered such a situation. This article captures the experience of one oncology nurse who underwent chemotherapy treatment for breast cancer at her place of employment. She discusses her cancer, chemotherapy treatments, and new level of understanding with patients. Her colleagues also share their reactions to witnessing the survivorship process. The nursing team at POHA has been inspired and humbled by the experience, and patient care has been enhanced. The courage of one individual's journey has demonstrated how a negative situation can be transformed into a positive one.

On how increasing numbers of newer cancer therapies further delay referral to hospice: the increasing palliative care imperative.

Delay in referral of cancer patients to hospice until very near the end of life may deny patients and families optimal palliative care. A variety of factors may contribute to these delays. This article describes how the proliferation of newer anticancer therapies, although desirable overall, may further increase these delays. It is important for hospice personnel to understand these changes in medical oncology and to work to optimize palliative care delivery concomitantly with disease-remitting therapies.

Administration of pemetrexed immediately following gemcitabine as front-line therapy in advanced non-small cell lung cancer: a phase II trial.

BACKGROUND: Pemetrexed and gemcitabine have demonstrated independent anti-tumor activity in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC). The combination of these two therapies may produce synergistic anti-tumor effects. Previous studies of this combination have included a 90-min separation between the two drugs. More recent preclinical studies have suggested that this delay in administration might be unnecessary. This phase II study was designed to determine the objective tumor response rate and toxicity when pemetrexed was administered immediately after gemcitabine on day 1. METHODS: Chemonaïve patients stage IIIB with pleural effusion or stage IV NSCLC were enrolled. Treatment consisted of gemcitabine 1250 mg/m2 (30-min intravenous infusion on days 1 and 8) and pemetrexed 500 mg/m2 (10-min i.v. infusion, immediately following gemcitabine, on day 1) every 21 days. All patients received folic acid, vitamin B12, and steroid prophylaxis. RESULTS: The 53 enrolled patients completed a total of 199 cycles (median=4.0, mean=3.8). Best tumor response consisted of 1 complete response (2.0%), 15 partial responses (30.6%), 17 with stable disease (34.7%), and 16 with progressive disease (32.7%). Median time to disease progression was 3.3 months and median survival was 10.3 months. Grades 3/4 hematologic toxicities (% patients) consisted of: neutropenia (43.4), anemia (9.4), febrile neutropenia (7.5%) and thrombocytopenia (1.9). The most common grades 3 or 4 non-hematologic events were: dyspnea (15.1), fatigue (11.3), and pyrexia (9.4). One patient (1.9%) experienced grade 2 alopecia. CONCLUSION: This schedule of pemetrexed plus gemcitabine is tolerable and offered the advantage of not requiring a 90-min delay between the two drugs. Response rate, survival, time to disease progression, and toxicity were acceptable and similar to other NSCLC regimens.

Chemotherapy-induced amenorrhea from adjuvant breast cancer treatment: the effect of the addition of taxanes.

PURPOSE: Adjuvant chemotherapy for breast cancer can be associated with a variety of side effects, one of which is the induction of premature menopause in premenopausal patient. Although taxanes have increasingly been used in the adjuvant setting, there has been relatively little published on the frequency of amenorrhea related to their use. PATIENTS AND METHODS: We review records of 159 premenopausal patients receiving adjuvant chemotherapy from our practice. RESULTS: Altogether, 51% of all patients retained menstrual function after chemotherapy. CONCLUSION: It was observed that patients receiving adjuvant anthracycline-based chemotherapy with sequential taxane therapy did not have a higher rate of amenorrhea than those not receiving a taxane.

Open-label study of pemetrexed alone or in combination with cisplatin for the treatment of patients with peritoneal mesothelioma: outcomes of an expanded access program.

BACKGROUND: To date, few large studies have been reported of patients with peritoneal mesothelioma, and treatment of this disease has been largely extrapolated from the treatment of pleural disease. Hence, it was considered important to study and report on this specific patient population. Before the regulatory approval of pemetrexed, an expanded access program (EAP) provided access to eligible patients with malignant pleural or peritoneal mesothelioma. PATIENTS AND METHODS: Patients received pemetrexed 500 mg/m2 alone or in combination with cisplatin 75 mg/m2 once every 21 days for > or = 6 cycles. All patients received folic acid, vitamin B12, and steroid prophylaxis. Serious adverse events (SAEs) were compiled in a pharmacovigilance database, which included all patients in the EAP with pleural or peritoneal mesothelioma. From June 12, 2002 to February 18, 2004, 1056 patients with malignant mesothelioma were enrolled and received > or = 1 dose of treatment at 462 sites in the United States. Of these patients, 98 (9.3%) had peritoneal mesothelioma (57 previously treated, 38 chemotherapy-naive, and 3 with missing data). RESULTS: Response data were available for 73 patients (43 previously treated, 28 chemotherapy-naive, and 2 not classified), indicating response rates of 23.3% for previously treated patients (0 complete responses [CRs], 10 partial responses [PRs], 21 cases of stable disease [SDs], 12 cases of progressive disease [PDs]) and 25% for chemotherapy-naive patients (3 CRs, 4 PRs, 12 SDs, and 9 PDs). Median survival was 13.1 months for previously treated patients and has not been reached for chemotherapy-naive patients. The most commonly reported SAEs for the total EAP were dehydration (7.2%), nausea (5.2%), and vomiting (4.9%). CONCLUSION: Pemetrexed with or without cisplatin had a favorable safety profile, and the disease control rate (CR + PR + SD) of 71.2% in the subset of patients with peritoneal mesothelioma indicated activity in this patient population.

On the need for biopsy confirmation at suspected first recurrence of cancer.

At the time of suspected first recurrence of cancer, it is unclear whether biopsy confirmation is routinely performed, although this is a very common clinical situation. First, 20 oncologists were surveyed to ascertain the pattern of practice in our community. A questionnaire with hypothetical typical cases suspected of having recurrent cancer was distributed. Second, eligibility criteria were reviewed from investigational protocols from the National Cancer Institute (NCI) and the Eastern Cooperative Oncology Group to see whether confirmation of recurrence was specifically required in these research studies. Third, 64 cases from our own practice were reviewed retrospectively to determine our patterns and results in performing biopsies to document suspected recurrence. Finally, criteria were developed that might suggest the need for biopsy confirmation of recurrence and then retrospectively tested against our cases. There was no clear consensus among oncologists regarding the need for tissue confirmation in patients with solid tumor with suspected recurrences, although rebiopsy was routinely requested for recurrent lymphoma. Published Eastern Cooperative Oncology Group and NCI protocols reviewed did not require biopsy proof specifically of recurrence. Retrospective review of our own cases suggested that, in the absence of one of the proposed indicators, the risk of making an erroneous diagnosis without biopsy confirmation is low. It is suggested that biopsy is not routinely necessary for confirmation of recurrence in all cases of suspected recurrent solid tumors, but criteria are proposed that would help to reduce the possibility of misdiagnosis when biopsy of suspected recurrence is not performed.

Phase II multicenter trial of albumin-bound paclitaxel and capecitabine in first-line treatment of patients with metastatic breast cancer.

BACKGROUND: Capecitabine, a tumor-activated oral fluoropyrimidine, and albumin-bound paclitaxel (ab-paclitaxel) have substantial single-agent activity in patients with metastatic breast cancer (MBC). Taxane and antimetabolite doublets have improved efficacy compared with single agents. This phase II open-label trial was designed to test the safety and efficacy of capecitabine and ab-paclitaxel in previously untreated MBC. PATIENTS AND METHODS: Patients received capecitabine (825 mg/m(2) orally twice daily, approximately 12 hours apart, on days 1 to 15) and ab-paclitaxel (125 mg/m(2) intravenously on days 1 and 8 of each cycle with no premedication) every 3 weeks. The primary endpoint was overall objective response rate (ORR), with evaluation performed after every 2 cycles. Entry criteria included measurable MBC, human epidermal growth factor receptor 2 (HER2) negativity, Eastern Cooperative Oncology Group (ECOG) performance status 0-2, no previous chemotherapy for metastatic disease, and > 6 months since adjuvant fluoropyrimidine or paclitaxel treatment. RESULTS: Fifty patients received at least 1 dose of study drug, with 46 patients evaluable for efficacy evaluation. Three hundred seventy-four cycles of therapy were delivered. Eighty percent of patients completed 8 cycles. The ORR was 61% (complete response [CR], 4%; partial response [PR], 57%), and 7 patients had sustained (≥ 24 weeks) stable disease for a clinical benefit rate of 76.1%. The median progression-free survival (PFS) was 10.6 months, and the median overall survival was 19.9 months. The most common adverse events (AEs) that were ≥ grade 3 were pain, hand-foot syndrome, and neutropenia. CONCLUSION: The combination of weekly ab-paclitaxel plus daily capecitabine orally at these doses and scheduling was well tolerated and showed substantial efficacy.

Drug-induced hematologic syndromes.

Objective. Drugs can induce almost the entire spectrum of hematologic disorders, affecting white cells, red cells, platelets, and the coagulation system. This paper aims to emphasize the broad range of drug-induced hematological syndromes and to highlight some of the newer drugs and syndromes. Methods. Medline literature on drug-induced hematologic syndromes was reviewed. Most reports and reviews focus on individual drugs or cytopenias. Results. Drug-induced syndromes include hemolytic anemias, methemoglobinemia, red cell aplasia, sideroblastic anemia, megaloblastic anemia, polycythemia, aplastic anemia, leukocytosis, neutropenia, eosinophilia, immune thrombocytopenia, microangiopathic syndromes, hypercoagulability, hypoprothrombinemia, circulating anticoagulants, myelodysplasia, and acute leukemia. Some of the classic drugs known to cause hematologic abnormalities have been replaced by newer drugs, including biologics, accompanied by their own syndromes and unintended side effects. Conclusions. Drugs can induce toxicities spanning many hematologic syndromes, mediated by a variety of mechanisms. Physicians need to be alert to the potential for iatrogenic drug-induced hematologic complications.

Promising survival in patients with recurrent non-small cell lung cancer treated with docetaxel and gemcitabine in combination as second-line therapy.

INTRODUCTION: Lung cancer is the leading cause of cancer death in men and women, and current second-line chemotherapy regimens yield relatively poor response and survival rates. HYPOTHESIS: We hypothesized that the combination of weekly docetaxel (D) and gemcitabine (G) would show activity in the second-line setting. We therefore conducted a phase II trial evaluating this regimen in patients with relapsed or progressive non-small cell lung cancer (NSCLC) after first-line platinum-based therapy. METHODS: Patients with recurrent NSCLC, adequate physiologic indices, and exposure to one prior platinum-based regimen were eligible. Docetaxel 40 mg/m intravenous (IV) and gemcitabine (G) 800 mg/m IV weekly were administered on day 1 and 8 every 21 days. In the absence of dose-limiting toxicity, G was escalated on an intrapatient basis to 1 g/m/wk. The primary endpoint was response rate (RR); event-free (EFS) and overall survival were secondary endpoints. RESULTS: Thirty-five patients (median age 61 years; 20 [57%] male) were accrued. Most (88%) had previously received carboplatin/paclitaxel, 31.4% in combination with a third investigational agent, more than half (57.1%) had prior radiation. The median number of cycles was four. RR was 23%. Median EFS was 5.7 months and median overall survival was 12.5 months. Patients who had their cancer diagnosed more than or equal to 12 months before entering the trial had superior EFS (13.7 months versus 4.8 months). Toxicity was acceptable. There were no treatment-related deaths. CONCLUSIONS: A nonplatinum doublet with GD is feasible and effective in the treatment of recurrent, platinum-exposed NSCLC patients. RR and survival are promising.

Pemetrexed alone or in combination with cisplatin in previously treated malignant pleural mesothelioma: outcomes from a phase IIIB expanded access program.

BACKGROUND: In a randomized phase III trial, pemetrexed plus cisplatin was associated with improved survival compared with cisplatin alone for patients with malignant pleural mesothelioma (MPM). However, there are limited data available on the efficacy of these and other chemotherapy regimens in patients who have received previous systemic chemotherapy. To gather additional efficacy and safety data of pemetrexed/cisplatin and pemetrexed alone in previously treated patients, we examined patients treated on the Eli Lilly and Company expanded access program (EAP). PATIENTS AND METHODS: Patients with malignant mesothelioma were enrolled in this trial. Of 1056 patients receiving at least one dose of the study drug, 187 (17.7%) were previously treated patients with MPM. Patients were treated every 21 days with pemetrexed 500 mg/m alone (n = 91) or in combination with cisplatin 75 mg/m (n = 96) for a maximum of six cycles. All patients received folic acid and vitamin B12 supplementation and steroid prophylaxis. Serious adverse events (SAEs) were reported by investigators and compiled in a pharmaco-vigilance database for all patients enrolled in the EAP. RESULTS: Median age of the previously treated pleural mesothelioma subset was 66 years (range, 27-87 years). Based on 153 evaluable patients (a subset of the larger intent-to-treat population of 187), the overall response rate was 32.5% for pemetrexed and cisplatin and 5.5% for pemetrexed alone. The disease control rate (response rate + stable disease) was 68.7% for pemetrexed and cisplatin and 46.6% for pemetrexed alone. Median survival was 7.6 months for pemetrexed plus cisplatin (67% censored) and 4.1 months for pemetrexed alone (55% censored). The most commonly reported serious adverse events in the overall EAP irrespective of causality were dehydration (7.2%), nausea (5.2%), vomiting (4.9%), dyspnea (3.8%), and pulmonary embolism (2.4%). CONCLUSIONS: The data from this EAP study suggest that patients with previously treated MPM can benefit from treatment with pemetrexed alone or in combination with cisplatin. The treatment is associated with acceptable toxicity.

Cancer of unknown primary: changing approaches. A multidisciplinary case presentation from the Joan Karnell cancer center of pennsylvania hospital.

Cancer of unknown primary is a common clinical syndrome, accounting for 2%-5% of cancer patients. A representative case is presented. This heterogenous group of disorders includes entities such as poorly differentiated carcinoma of unknown primary, adenocarcinoma of unknown primary, neuroendocrine carcinoma of unknown primary, squamous cell carcinoma of unknown primary, poorly differentiated (not otherwise specified) cancer of unknown primary, and melanoma of unknown primary. It is crucial to identify those treatment-responsive presentations of unknown primary with the greatest potential for long-term survival. This discussion emphasizes newer approaches to the diagnosis and treatment of unknown primary cancer, including advances in pathology with immunoperoxidase and molecular genetic techniques, positron emission tomography, and published chemotherapeutic trials. With the increased sophistication of pathologic and radiologic techniques, the frequency of unknown primary cancers will likely continue to decline. Further, as newer and more targeted therapies for specific types of cancer are identified, the previously held nihilism regarding the search for and identification of the primary may become less supportable.