Early radiographic response to epidermal growth factor receptor-tyrosine kinase inhibitor in non-small cell lung cancer patients with epidermal growth factor receptor mutations: A prospective study.

BACKGROUND: The time schedules for response evaluation of epidermal growth factor receptor-tyrosine kinase Inhibitor (EGFR-TKI) in non-small cell lung cancer (NSCLC) patients are still ill-defined. METHODS: Stage IIIB/IV patients with histologically proven NSCLC were enrolled in this study if the tumor cells bore EGFR mutations other than T790M. Eligible patients were treated with either 250 mg of gefitinib or 150 mg of erlotinib once daily. The early response rate [computed tomography (CT) scan on Day 14], definitive response rate determined on Day 56, progression-free survival (PFS), overall survival (OS), and toxicity profile were assessed prospectively. RESULTS: Thirty-nine patients were enrolled in this study. A total of 29 patients (29/39, 74.4%) achieved partial response (PR). Twenty-one patients (21/39, 53.8%) had early radiological response on Day 14. The early radiological response rate in patients with PR was 72.4% (21/29). Only eight patients without a PR on early CT still ended with PR. Among the 29 patients with PR, the PFS (8.1 months) and OS (18.3 months) of the 21 patients with early CT response were shorter than those of the 8 patients without early CT response (11.9 and 24.0 months for PFS and OS, respectively). But the survival differences were statistically non-significant. CONCLUSIONS: A very high percentage (72.4%, 21/29) of NSCLC patients with EGFR mutations with PR demonstrates early radiological response to EGFR-TKIs, which would advocate early radiological examination for EGFR-TKI therapy in NSCLC patients.

Culture supernatants of different colon cancer cell lines induce specific phenotype switching and functional alteration of THP-1 cells.

We developed an in vitro model to evaluate the effect of products secreted from different colorectal cancer (CRC) cell lines on specific phenotypic switching and functional alterations in THP-1 cells. We co-cultured the human monocytic cell line, THP-1, or phorbol-12-myristate-13-acetate (PMA)-treated THP-1 cells, (THP-1p), with supernatants from either the HT-29 (Dukes' B), HCT-15 (Dukes' C), or Colo205 (Dukes' D) cell lines, and assessed the cells for macrophage differentiation. The surface marker and cytokine profiles suggested that secreted CRC factors differentiated THP-1 cells into a "mixed" M1/M2 phenotype, although HT-29 and Colo205 supernatants induced THP-1p cells into predominantly M1-like macrophages and M2-like macrophages, respectively. Further, all three CRC supernatants enhanced the phagocytic capacity and migration of THP-1 and THP-1p cells, altering their phenotype to a more M2-kind. Therefore, different CRC cell lines induced specific phenotype switching and functional polarization of THP-1 cells.

Sunitinib in metastatic renal cell carcinoma: an ethnic Asian subpopulation analysis for safety and efficacy.

AIMS: We evaluated and compared the safety and efficacy of sunitinib in Asian and non-Asian patients with metastatic renal cell carcinoma enrolled in a previously reported global expanded access program. METHODS: Previously treated and treatment-naïve patients received open-label sunitinib at a starting dose of 50 mg/day for 4 weeks, followed by 2 weeks off treatment, in repeated 6-week cycles. Safety was assessed regularly, tumor measurements were performed per local practice, and survival data collected where possible. RESULTS: Data were available for 212 Asian patients from Asian sites (Asian-A), 113 Asian patients from non-Asian sites (Asian-O) and 4046 non-Asian patients. The most common grade 3/4 treatment-related adverse events were neutropenia, thrombocytopenia, hand-foot syndrome, diarrhea, asthenia and fatigue. The incidence of many adverse events was greater in Asian-A than in Asian-O or non-Asian patients. Sunitinib efficacy was comparable between Asian and non-Asian patients, with an objective response rate of 18% versus 14%; median progression-free survival of 8.7 versus 10.9 months; and overall survival of 18.9 versus 18.4 months, respectively. CONCLUSIONS: Sunitinib demonstrated tolerable safety and similar efficacy in Asian and non-Asian patients. Geographic differences in the reported frequency of specific adverse events were noted across Asian patients.

Omega-3 fatty acid-, micronutrient-, and probiotic-enriched nutrition helps body weight stabilization in head and neck cancer cachexia.

OBJECTIVE: To evaluate whether an oral nutritional supplement enriched with omega-3 fatty acids, micronutrients, and probiotics affected body weight (BW) changes, serum albumin and prealbumin levels in patients with head and neck cancer (HNC) cachexia. STUDY DESIGN: Sixty-eight HNC patients were randomly assigned to receive either an Ethanwell/Ethanzyme (EE) regimen enriched with omega-3 fatty acids, micronutrients, and probiotics, or control (Isocal) for a 3-month period. Analysis of covariance was used to examine the association between BW change and variables. RESULTS: Patients with body mass index (BMI) <19 and those receiving the EE regimen consumed fewer daily calories but showed significantly increased BW and maintained higher serum albumin and prealbumin levels than other patients (P<.05). Their BW changes were significantly associated with changes in serum albumin and prealbumin levels. CONCLUSIONS: EE regimen improved BW as well as serum albumin and prealbumin levels in HNC patients with BMI <19.

Low-dose zoledronic acid reduces spinal cord metastasis in pulmonary adenocarcinoma with neuroendocrine differentiation.

Zoledronic acid (ZOL), a nitrogen-containing compound, is effective in the treatment of skeletal disorders, but its long-term use in high doses gives rise to complications such as osteonecrosis. We aimed to investigate the effect of low-dose ZOL on the expression of the neural cell adhesion molecule (NCAM), which may be correlated with tumor growth and spinal cord metastasis in lung adenocarcinoma with neuroendocrine differentiation. First, we used the small hairpin RNA technique to directly knock down NCAM expression in cells of a murine lung adenocarcinoma line, line 1 cells, and found that the tumor cells generated showed lower invasive capacity, slower tumor growth, and lesser tendency for spinal cord metastasis than control cells. Further, ZOL decreased NCAM expression and invasiveness in line 1 tumor cells in vitro. Line 1/lacZ cells, a stable clone tagged with the lacZ gene, were introduced into mice, followed by ZOL treatment (1 µg/kg/weekly). Low-dose ZOL significantly reduced spinal cord metastasis probably through reduced NCAM expression in vivo. These findings indicated that NCAM is involved in tumor growth and spinal cord metastasis of lung adenocarcinoma with neuroendocrine differentiation. Treatment with low-dose ZOL can reduce NCAM expression that may contribute toward reduced spinal cord metastasis, suggesting that NCAM is an alternative therapeutic target and that the low-dose ZOL treatment protocol is a reasonable approach for its treatment.

Epidermal growth factor receptor mutations in patients with oral cavity cancer in a betel nut chewing-prevalent area.

BACKGROUND: Epidermal growth factor receptor (EGFR) mutations exist in patients with oral cavity squamous cell carcinoma (OSCC), but few data about mutation patterns with clinical outcomes were reported. METHODS: Fifty-six formalin-fixed paraffin-embedded tumor samples were obtained surgically from OSCC patients. Direct sequencing of EGFR was carried out using nested polymerase chain reaction. The relationship between EGFR status and clinical courses was analyzed. RESULTS: Two (3.56%) missense mutations (G857R; L862Q) in exon 20 were identified. Two types of silent mutation, A859A in exon 21 (1.79%) and Q787Q mutations in exon 20 (30.36%), were also found. No mutation was detected in exons 18 and 19. No significant difference in disease-free survival and locoregional control rate was shown between patients with and without Q787Q mutation. CONCLUSIONS: We identified a high frequency of Q787Q mutation and a less prevalent active EGFR mutation in OSCC patients in Taiwan where betel nut is commonly chewed.

Tumor growth inhibition of metastatic nasopharyngeal carcinoma cell lines by low dose of arsenic trioxide via alteration of cell cycle progression and induction of apoptosis.

BACKGROUND: Although arsenic trioxide (ATO) has displayed anticancer activity against primary nasopharyngeal carcinoma (NPC), its efficacy in metastatic NPC deserved further investigation because the biological/therapeutic difference in cancer cells probably exists between primary and distant sites. METHODS: Two human metastatic NPC cell lines (NPC-BM1 and NPC-BM2) were investigated. We measured cellular proliferation, cell cycle, and apoptotic extent of BM1 and BM2 cells treated with ATO in vitro. Furthermore, we evaluated the tumor growth after ATO treatment in vivo. RESULTS: Low-dose ATO treatment is sufficient to induce an antiproliferative effect, alter the cell cycle, and increase apoptosis in BM1 and BM2 cells. BM1 tumor growth in a xenograft model with low-dose and short-schedule (1 mg/kg/day, intraperitoneal injection for 5 consecutive days) of ATO treatment significantly slowed in vivo. CONCLUSION: ATO at low dose seems to be an encouraging schedule for palliative treatment of metastatic NPC.

Zoledronic acid induces cell-cycle prolongation in murine lung cancer cells by perturbing cyclin and Ras expression.

Zoledronic acid (ZOL) was shown earlier to prolong survival in animal models of lung cancer. The aim of this study was to examine whether alteration of intracellular cyclins, cyclin-dependent kinases, cyclin-dependent kinase inhibitors, retinoblastoma, and Ras protein expression and E2F localization are among the possible antilung cancer mechanisms driven by ZOL. Furthermore, we used geranylgeraniol to test whether the mevalonate pathway is involved in the antitumor effects of ZOL against lung cancer. Line-1 cells, a murine lung adenocarcinoma cell line, were examined. ZOL significantly slowed the growth of these cells both in vitro and in vivo. The ZOL-treated cells typically arrested at the S/G2/M phase of the cell cycle, accompanied by increased intracellular levels of cyclin A, B1, and CDC2 and decreased levels of cyclin D, p21, p27, phosphorylated retinoblastoma, and Ras. In addition, ZOL affected the distribution of E2F. When geranylgeraniol was added to the ZOL-treated cells, either in vitro or in vivo, tumor growth, cell-cycle progression, the expression of certain cyclins, and cyclin-related regulatory proteins were partially returned to that of untreated controls. Therefore, ZOL elicits cell-cycle prolongation that seems to be associated with alterations in the levels of certain cyclins and cyclin-related regulatory proteins. Furthermore, the mevalonate pathway regulates ZOL-induced murine lung cancer inhibition both in vitro and in vivo.

Neutralization of interleukin (IL)-10 released by monocytes/macrophages enhances the up-regulatory effect of monocyte/macrophage-derived IL-6 on expressions of IL-6 and MUC1, and migration in HT-29 colon cancer cells.

The interactions between monocyte-derived IL-6 and IL-10 in colon cancer are unknown. We continued previous work that showed monocyte/macrophage-derived IL-6 induces IL-6 and MUC1 expression in HT-29 cancer cells, and evaluated if IL-10 present in monocyte/macrophage is involved in this IL-6-mediated effect. We treated HT-29 cells with monocyte/macrophage supernatant following neutralization of monocyte/macrophage-released IL-10. Neutralization markedly enhanced monocyte/macrophage-derived IL-6 effects on HT-29 cells including IL-6 and MUC1 production and cell migration. Double blocking of IL-6 and IL-10 in monocyte/macrophage supernatants abolished this enhancement. Western blot analysis of STAT3 phosphorylation showed that this augmented response in HT-29 cells following IL-10 neutralization is probably mediated through enhanced IL-6-induced phosphorylation (Tyr(705)) of STAT3 proteins. Therefore, monocytes/macrophages have the capacity to release the functionally associated cytokines IL-6 and IL-10 whose interactions can account for the pathogenesis and progression of colon cancer.

Using vital sign flow sheets can help to identify neoplastic fever and other possible causes in oncology patients: a retrospective observational study.

CONTEXT: It is important to determine the etiology of fever in cancer patients. Such patients often undergo extensive laboratory and radiographic investigations and prolonged anti-infective therapy that are time- and resource- consuming, risk drug toxicity, and postpone systemic chemotherapy. OBJECTIVES: To investigate neoplastic fever (NF) patterns from vital sign flow sheets. METHODS: Between September 1997 and February 2009, data on 150 consecutive hospitalized patients with advanced or metastatic solid tumors documented to have NF were retrospectively collected. Sixty patients with sepsis were used as a comparison group. RESULTS: All patients with NF demonstrated intermittent fever patterns. Peak body temperature was 39.0+/-0.6 degrees C (38.0-40.8 degrees C). Baseline pulse rates in 139 (93%) patients showed no increase except during febrile periods. The remaining 11 (7%) patients had transiently elevated baseline pulse rates at the time of cessation of postchemotherapy dexamethasone. Once-daily fever spike patterns occurred in 108 (72%) patients. Fever spikes were most commonly found at 9 am (42%) and 5 pm (37%). Twice-daily fever spike patterns were noted in the 42 (28%) remaining patients. In the comparison group, baseline pulse rate elevated in all patients during febrile periods and 20 (33%) showed intermittent fever patterns. CONCLUSION: We conclude that the NF pattern is characterized by intermittent fever without an obvious increase in baseline pulse rate except during febrile periods. Knowing NF patterns from vital sign flow sheets can help identify NF and other possible causes of fever in oncology patients.

Immunotherapy with dendritic cells pulsed by autologous dactinomycin-induced melanoma apoptotic bodies for patients with malignant melanoma.

The primary goal of this study was to evaluate the efficacy of immunotherapy for patients with metastatic melanoma with autologous melanoma apoptotic bodies (MAB)-pulsed dendritic cells (DCs). Accessible tumors from eligible patients with refractory metastatic melanoma were surgically removed and processed for primary culture. The autologous tumor cells were treated with dactinomycin to obtain MAB. To generate DCs, adherent peripheral blood mononuclear cells were cultured in complete medium containing granulocyte macrophage-colony stimulating factor and interleukin-4. MAB-pulsed DCs were given either intradermally (i.d.) or intravenously. Patients were immunized at monthly intervals and boosted with keyhole limpet hemocyanin (KLH) and MAB 2 weeks post-vaccination, with a maximum of four cycles. Of the 10 patients enrolled in this trial, nine were treated with MAB-pulsed DCs; two were given intravenous vaccinations and the other seven were i.d. injected. Mild tenderness in the draining lymph nodes lasting for less than 48 h and enlargement of the draining lymph nodes were noted in all seven i.d. cases. Treatment-related grade 3-4 toxicity, neutropenia, skin ulceration, tumor growth at the injection site, and sepsis were not observed in any of the patients. Delayed-type hypersensitivity to KLH was observed in all patients, whereas no delayed-type hypersensitivity to autologous tumor antigens was observed. One patient achieved partial response with reduction in lung metastatic tumor mass, and a presence of vesicles in the post-vaccination KLH response. Two patients had stable disease for more than 24 months; one was still alive at the time of submission of this report, the other eventually developed multiple metastases. MAB-pulsed DC immunotherapy is well tolerated in patients with malignant melanoma; however, its efficacy is only modest. Combination with other modalities is required to enhance DC-based immunotherapy.

Phase II study of epirubicin in combination with weekly docetaxel for patients with advanced NSCLC who have failed or relapsed after the frontline platinum-based chemotherapy.

BACKGROUND: We conducted a phase II study to evaluate the efficacy and toxicity of weekly docetaxel combined with epirubicin on D15 as second-line chemotherapy in Taiwanese patients with advanced non small cell lung cancer (NSCLC) who failed or relapsed after the frontline platinum-based chemotherapy. PATIENTS AND METHODS: Patients with histologically confirmed advanced NSCLC (Stage IIIB-IV) were entered into this Phase II trial. Eastern Cooperative Oncology Group performance status was 0 to 2 and adequate organ function was required. Docetaxel, 30 mg/m, was given intravenously on days 1, 8, and 15 for 30 minutes and epirubicin, 60 mg/m, was given intravenously on day 15, then following one week of rest. Treatment was repeated every 4 weeks for a maximal total of 6 cycles. RESULTS: Of the 43 eligible patients, 39 patients were evaluated for response, and all were evaluated for toxicity. The overall response rate was 11.6% [95% confidence interval (CI), 1.6-21.6%]. The median time to disease progression for all patients was 2.8 months (95% CI 1.3-4.3%). The median survival time for all patients was 7.7 months (95% CI 5.5-9.9%). The 1-year survival was 32.6% (95% CI 25.4%-39.7%). The major hematologic toxicities were neutropenia, 8/43 (19%) with grade 3-4 neutropenia, as well as anemia, 6/43 (14%) with grade 3-4 anemia. Nonhematological toxicities were modest. Fatigue was common, 77.8% in all, but only 3 (7%) patients with grade 3-4 toxicities. Diarrhea was also common but not severe, 7/43 (16%) with grade 1-2 episodes, and 1/43 (2%) with grade 3-4 episodes. Nail changes, peripheral edema, lacrimation, and alopecia were mild. Hepatic and renal impairment was also only mild. CONCLUSION: Combining weekly doses of docetaxel 30 mg/m with epirubicin 60 mg/m on D15 was not shown to improve both efficacy and tolerability for advanced NSCLC patients who have relapsed disease after frontline platinum-based chemotherapy.

Zoledronic acid is unable to induce apoptosis, but slows tumor growth and prolongs survival for non-small-cell lung cancers.

BACKGROUND: Although zoledronic acid (ZOL), a third-generation nitrogen-containing bisphosphonate, has been identified as an attractive therapeutic agent against breast cancer, prostate cancer, multiple myeloma as well as small-cell lung cancer (SCLC), as best as we are aware, the anti-tumor effect of ZOL upon non-small-cell lung cancer (NSCLC) remains to be effectively investigated. This study examined the effects of ZOL upon the line-1 tumor cell, using a murine lung adenocarcinoma cell line similar to the behavior of human lung adenocarcinoma. METHODS: We investigated the anti-tumor effects of ZOL (3-100 microM) on line-1 tumor cells in vitro, including cellular proliferation, by means of an MTT assay, cell-cycle analysis by flow cytometry and by assessing the level of apoptosis by annexin V/propidium iodide (PI) and 4'-6-diamidino-2-phenylindole (DAPI) staining. Further, we evaluated the growth and survival of line-1 tumor cells following ZOL treatment (1 microg/kg/week) using an animal model. We also examined the in vivo cell-cycle pattern using lacZ-expressing line-1 cells (line-1/lacZ). RESULTS: ZOL significantly slowed the line-1 tumor growth in a dose-dependent manner in vitro. The treated line-1 tumor cells typically arrested at the S/G2/M-phase of the cell-cycle following ZOL exposure, but no apoptotic cells could be detected by either annexin V/PI or DAPI staining. When the ZOL was washed out, the drug-inhibited cells continued to proliferate again and the cell-cycle prolongation elicited earlier by the drug, then disappeared. Within 72-96 h following drug removal, the cell-cycle of the treated cells revealed a similar distribution to that of the untreated controls. In vivo studies demonstrated that ZOL significantly slowed the line-1 tumor growth. Indeed, mice lived significantly longer when they had been ZOL-treated than was the case for untreated mice (p<0.05). Using line-1/lacZ cells, the in vivo cell-cycle distribution of line-1 tumor cells subsequent to ZOL exposure revealed S/G2/M-phase arrest that was identical to the in vitro culture. CONCLUSIONS: ZOL maintains the potential to reduce tumor burden and prolong survival for murine pulmonary adenocarcinoma. The flow cytometrical analysis of cell-cycle demonstrated that ZOL induces no apoptosis but is able to arrest line-1 tumor cells at the S/G2/M-phase. Although the clinical relevance of these results warrants verification for human lung cancer patients, ZOL combined with chemotherapy and/or radiotherapy appears to be a new therapeutic strategy for the effective treatment of NSCLC.

Phase II study of a biweekly regimen of vinorelbine and cisplatin in advanced non-small cell lung cancer.

BACKGROUND: Many novel agents, including vinorelbine, gemcitabine, paclitaxel and docetaxel, have been administrated in combination with cisplatin to patients with advanced non-small cell lung cancer (NSCLC). Of these drugs, vinorelbine is reported to have a high response rate and acceptable toxicity level. In an attempt to increase treatment activity, a biweekly regimen using vinorelbine and cisplatin was designed. METHODS: From March 2001 to July 2003, 43 patients with NSCLC, who met the selection criteria, were enrolled. Of the 43 patients, 28 were male and 15 were female. All of them had their diagnosis confirmed histologically and were in an advanced stage, i.e., stage IIIB with pleural effusion or stage IV. Vinorelbine 30 or 35 mg/m2 and cisplatin 50 mg/m2 were given intravenously every 2 weeks. RESULTS: Of the 43 assessable patients, 11 achieved a Partial Response (PR) and 13 had a Stable Disease (SD). Overall response was 25.6% (95% CI 12.0%-39.2%). Median survival was 9.0 months (95% CI: 6.2-11.8) and the 1-year survival rate was 32.6%. Median time to disease progression was 3.9 months (95% CI 2.4-5.4 months). The major hematological toxicity was neutropenia. Seven patients (16.3%) developed grade 3 neutropenia and 17 patients (39.5%) developed grade 4 neutropenia. Eight patients developed febrile neutropenia, 4 patients had confirmed sepsis, 2 of which died due to sepsis. One patient had grade 3 thrombocytopenia. Six patients (7%) developed severe anemia. Ten patients (23.3%) had grade 3/4 nausea and vomiting. Only 2 patients developed grade 3 neuropathy. CONCLUSIONS: This biweekly regimen of vinorelbine and cisplatin is effective against advanced NSCLC. Due to the high incidence of neutropenia, this regimen did not improve therapeutic efficacy and its dose intensity is less than that of a conventional schedule.

Regressed subungual melanoma simulating cellular blue nevus: managed with sentinel lymph node biopsy.

BACKGROUND: Subungual melanoma, a not uncommon presentation of cutaneous melanoma in Asian populations, is easily overlooked as benign and thus is improperly treated. OBJECTIVE: To present two cases with clinical suspicion of subungual melanoma. Skin biopsies failed to demonstrate the diagnostic features of malignancy. METHODS: Lymphoscintigraphy and sentinel lymph node (SLN) biopsies were performed to determine regional lymph node status. RESULTS: Both hematoxylin-eosin and HMB45 staining revealed melanoma cells in the SLN of the patient. The second patient's SLN was negative for malignant cells, but her excised primary lesion showed extensive regressed melanoma. CONCLUSION: Regression phenomena are not uncommon for subungual melanoma. An extention biopsy techniques are useful for determining nodal basin status in regressed subungual melanoma.

Weekly short infusion of taxotere at a 4 week cycle in Chinese patients with advanced NSCLC who have failed or relapsed after the frontline platinum-based non-taxane chemotherapy--a Phase II trial.

BACKGROUND: This Phase II study was conducted to evaluate the efficacy and toxicity of weekly docetaxel at a 4 week cycle in second-line therapy for patients with advanced non-small cell lung cancer (NSCLC) who failed to respond or relapsed after the frontline platinum-based, non-taxane regimen. METHODS: Patients with histologically confirmed and progressive NSCLC after one platinum-based, non-taxane regimen were eligible for this study. Performance status of 0-2 and adequate organ function were required. Patients were treated with docetaxel 40 mg/m(2)/week for three consecutive weeks then following 1 week of rest. Cycles were repeated every 4 weeks for a maximum total of six cycles. Docetaxel was administered intravenously for 30 min with dexamethasone premedication. RESULTS: Fifty-three patients were eligible for this study. Hematologic toxicity was very mild and with the major toxicity of anemia. Non-hematologic toxicities were modest, Grades 3-4 mucositis, diarrhea and peripheral neuropathy occurred in 6-13% of patients and caused dose modifications. Fatigue (48%) was common but not severe with only 6% of Grades 3-4 toxicity. The overall response rate (ORR) was 13% [95% confidence interval (CI), 3.9-23%]. The median survival time (MST) for all patients was 25.0 weeks (95% CI, 12.7-37.3), and the 1 year survival was 31% (95% CI, 17-58%). For patients with PS 0-1, MST was 29.7 weeks and 1 year survival was 36%. CONCLUSIONS: Weekly docetaxel appeared to be well tolerated as second-line therapy for patients with NSCLC. The efficacy for this regimen was comparable with the standard 3 week schedule but hematologic toxicity was markedly reduced. A schedule of three consecutive weeks, with a 1 week break, may diminish the frequency of fatigue and diarrhea when compared with a schedule of six consecutive weeks.

Dose-finding and phase 2 study of weekly paclitaxel (taxol) and cisplatin combination in treating Chinese patients with advanced nonsmall cell lung cancer.

OBJECTIVES: The aim of the present study is to evaluate the efficacy and toxicity of weekly paclitaxel combined with cisplatin as first-line chemotherapy in patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) and to identify the optimal dose of weekly paclitaxel to be administered safely and effectively. METHODS: Chemonaive patients with NSCLC, stage 3B with malignant pleural effusion, or stage 4 were enrolled in this study. In the dose-finding study, patients took paclitaxel once weekly at an initial dose of 50 mg/m2 and 3 weeks followed by cisplatin on day 15 at a fixed dose of 80 mg/m2. The escalating dose for paclitaxel was 10mg/m2 for each level. In the phase 2 study, patients received paclitaxel at maximum tolerated dose (MTD). RESULTS: The MTD for paclitaxel was 60 mg/m2. Of the 47 eligible patients, 7 patients had a complete response and 15 achieved a partial response. The overall response was 46.8% (95% CI, 32.0% to 61.6%). The median survival was 16 months (95% CI, 13.4 to 18.6 months). Twenty-four patients (51.1%) completed 6 cycles of treatment. With regard to hematological toxicity, although grade 3/4 neutropenia was observed in 5 patients (10.6%), there was no febrile neutropenia. The major nonhematological toxicity was asthenia, which was observed in all patients (17 patients grade 1/2 and 30 patients with grade 3/4). CONCLUSIONS: Weekly paclitaxel combined with cisplatin on day 15 is a safe and effective regimen as a first-line chemotherapy in NSCLC. The MTD for this regimen was 60 mg/m.

Ovarian metastasis originating from bronchioloalveolar carcinoma: a rare presentation of lung cancer.

Ovarian metastasis originating from bronchioloalveolar carcinoma (BAC) has not been reported previously. We report a 63-year-old Chinese woman who was diagnosed as BAC with pleural metastasis in 1997. Four years later, she complained of vaginal bleeding, and a pelvic mass was discovered by an abdominal computerized tomography scan. Tumor debulking and total hysterectomy with bilateral salpingo-oopherectomy were performed. Pathology disclosed well-differentiated adenocarcinoma, with abundant clear cytoplasm, in the ovaries. Furthermore, immunohistochemical staining revealed that the tumor cells from the ovary and pleura were reactive to thyroid transcription factor 1 (TTF-1) and cytokeratin-7 (CK-7) but were negative for cytokeratin-20 (CK-20). The results of immunohistochemical staining, clinical course, and pathological features were compatible with the diagnosis of BAC with ovarian metastasis. In conclusion, to investigate the primary site of a metastatic ovarian cancer, clinicians should not forget the lungs since the incidence of lung cancer in females is increasing. Moreover, a monoclonal antibody panel for TTF-1, CK-7, and CK-20 may facilitate discrimination between primary and metastasized ovarian adenocarcinomas and/or identifying tumors of pulmonary origin.