First-line systemic treatment with gefitinib in stage IV non-small cell lung cancer

Lung cancer has a high mortality rate and is often diagnosed in locally advanced or metastatic stages. A new therapeutic option for patients with non-small cell lung cancer (NSCLC) in these stages with progress or relapse after platinum-based chemotherapy exists in the inhibitors of the epidermal growth factor receptor (EGFR) tyrosine-kinase. EGFR tyrosine-kinase inhibitor treatment might also be an option for patients ineligible for surgery and conventional chemotherapy. We present a case of a 53-year-old woman who was diagnosed due to pain from multiple bone metastases of a lung adenocarcinoma. She refused cytotoxic chemotherapy, and we administered first-line systemic treatment with gefitinib subsequent to radiotherapy of metastatic bone disease. The patient responded well to gefitinib treatment and achieved a partial response after 3 weeks. No relevant side effects occurred, and the patient experienced an 8-month remission of disease. With a follow-up of 10 months, the patient is still alive. Retrospectively, we found a mutation of the EGF receptor in tumor cells of the patient, which is associated with sensitivity to gefitinib. EGFR tyrosine-kinase inhibitors (TKI) can be an alternative first-line systemic treatment option for selected patients with metastatic NSCLC.     

肺癌病人放射性核素骨显像

本文利用放射性核素骨显像研究56例肺癌的骨转移情况。其阳性率为62％,肺癌病人骨显像阳性发现早,常在术前及术后8个月以内,且常为多发灶。骨显像被认为是一高灵敏而非特异的检查骨转移的方法,故需仔细判断骨显像中所示阳性区域病灶。可使其假阳性降低为零。骨显像所示骨转移尤其是“隐匿性骨转移”似应与传统骨转移灶相区分,并对其性质、预后及治疗方法进行深入研究,从而使肺癌病人的骨转移得到早期、合理的治疗。     

Steatocystoma multiplex as initial impression of non-small cell lung cancer with complete response to gefitinib

Cutaneous metastases are rare and seldom present at the time of first diagnosis of cancer. Data from various studies show that 1-12% of lung cancer patients experience tumor spread to the skin. The scalp, chest, and abdomen are favored sites of skin metastases from lung cancers, but metastases to multiple skin sites in a single patient are rarely reported. We describe a 56-year-old lung adenocarcinoma patient, initially diagnosed with steatocystoma multiplex who responded well to gefitinib treatment. The efficacy of conventional chemotherapy for cutaneous metastases has been limited because of the relatively poor blood supply to the skin. It has been demonstrated that tyrosine kinase inhibitor (TKI), gefitinib, has significant clinical benefit in lung cancer patients with epidermal growth factor receptor (EGFR) mutation even in metastases to the brain. However, the therapeutic response to gefitinib in patients with skin metastases is seldom mentioned in the literature. We report one case of lung adenocarcinoma with multiple skin metastases that were successfully treated with gefitinib.     

Two cases of leptomeningeal metastases from lung adenocarcinoma which progressed during gefitinib therapy but responded to erlotinib

We present two patients with leptomeningeal metastases (LM) from lung adenocarcinoma that progressed or newly developed, respectively, during gefitinib therapy which had exhibited substantial antitumor effects on widespread lesions. In both cases, a switch to erlotinib therapy brought about long-lasting dramatic symptomatic improvement and markedly prolonged survival. The first patient is a 46-year-old female who presented with progressive headache and vomiting. Multiple pulmonary, hepatic and bone metastases immediately shrank in response to gefitinib. However, 1?month after completion of concurrent whole brain radiation, dizziness and urinary retention newly emerged, worsening the symptoms observed at presentation. Magnetic resonance imaging (MRI) demonstrated enlargement of ventricles and new gadolinium (Gd)-enhanced disseminated nodules on the surface of the cerebral cortex, suggesting the existence of uncontrollable LM. Sequential erlotinib therapy resulted in symptomatic improvement with a finding of regression of Gd-enhancement on MRI. The beneficial effect lasted for 10?months, though a follow-up brain MRI showed further enlarged ventricles. She finally died due to LM after surviving for 11?months under erlotinib treatment. The other patient is a 55-year-old female in whom headache and vomiting occurred while gefitinib therapy had maintained shrinkage of all pre-existing tumors in the thorax and bones. Brain MRI strongly suggested occurrence of LM with a finding of Gd-enhanced sulci. A switch to erlotinib therapy relieved the symptoms with disappearance of Gd-enhancement. However, the symptoms recurred with a finding of further enlargement of ventricles on brain MRI after 11?months. Finally, she died due to LM after surviving for 12?months under erlotinib treatment.     

Brain metastasis responding to gefitinib alone

A woman with stage IIIb non-small cell lung cancer (NSCLC) developed disease progression with brain metastases during chemotherapy. Due to unusual circumstances, the patient received gefitinib alone, without the use of corticosteroid treatment or radiotherapy. There was a dramatic clinical improvement within 1 week. Follow-up magnetic resonance imaging of the brain 1 month later showed decreases in both the size and number of brain metastases. The patient remains well 9 months after initiation of gefitinib. It is proposed that gefitinib may have a role in treatment of brain metastases from NSCLC.     

Long-term effect of gefitinib (ZD1839) on squamous cell carcinoma of the lung

This case report describes the effects of long-term treatment with the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) gefitinib ('Iressa', ZD1839) on a patient with squamous cell carcinoma of the lung. Gefitinib is an orally active agent that blocks signal transduction pathways implicated in the proliferation and survival of cancer cells and host-dependent processes that promote tumor growth. A 62-year-old Japanese man with a history of heavy smoking was diagnosed with squamous cell carcinoma of the lung, clinical stage IIIB (T4N3M0), in August 2000. He received two cycles of cisplatin-based chemotherapy and subsequently underwent left upper lobectomy followed by thoracic radiotherapy. After these treatments, he underwent partial lobectomy and pneumonectomy because of disease recurrence. In June 2002, he started treatment with gefitinib 250 mg/day orally because of mediastinal lymph node recurrence and an elevated serum cytokeratin 19 fragment (CYFRA) level. As a result, the mediastinal lymph node markedly regressed and the serum CYFRA level became normalized. Although he experienced recurrence three times during the 18 months prior to treatment with gefitinib, recurrence has not been experienced in the 13 months since the start of gefitinib treatment, while tolerability has been acceptable.     

A case report of synchronous small cell lung cancer and gastric cancer successfully treated with carboplatin

A 53-year-old man complained of anorexia and abdominal distention of one month's duration. The chest X-ray demonstrated a mass in the left lung with hilar and mediastinal adenopathy and a lytic lesion in the right fourth rib. A transbronchoscopic biopsy of the mass revealed oat cell carcinoma (WHO classification). The endoscopic evaluation also revealed a gastric lesion (IIc type). Biopsy of this lesion indicated signet ring cell gastric cancer. An abdominal CT scan demonstrated multiple liver metastases. Based on these findings, the patient was diagnosed as having synchronous lung and gastric primaries, with liver and bone metastasis from lung cancer. Carboplatin (CBDCA) was administered by intravenous drip infusion of 450 mg/m2. After a second treatment with CBDCA about 3 weeks later, the patient achieved a partial response at the primary site of lung cancer as well as at the liver and bone metastases. In addition, repeat endoscopy of the stomach demonstrated a complete regression. A biopsy specimen taken by gastroscopy was negative for cancer cells. Subsequent chemotherapy for small cell lung cancer was administered with cyclophosphamide, adriamycin, and vincristine, and to date there is no evidence of recurrence. Further studies on CBDCA treatment of small cell lung cancer and gastric cancer are needed to establish the efficacy of this drug against these two histologically different cancers.     

Sequential occurrence of small cell and non-small lung cancer in a male patient: Is it a transformation?

Lung cancer is one of the leading causes of cancer-related mortality and is categorized into small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). We present a patient with epidermal growth factor receptor (EGFR)-mutant-NSCLC who developed metastatic SCLC after initial therapy with second-generation EGFR-tyrosine kinase inhibitor, afatinib. A 65-year-old male non-smoker was diagnosed with adenocarcinoma of the right lung, stage IVA (M1a). Due to tumor positivity for EGFR-Exon 19 deletion, the patient was started on oral afatinib, which resulted in a partial response. After ten months of treatment, he presented in the office with abdominal pain, distension, weight loss and jaundice. He had diffuse skeletal and hepatic metastases on PET/CT scan with interval progression of his cancer. Although the recurrence of lung adenocarcinoma was suspected, the patient was diagnosed with SCLC on liver biopsy. He received two cycles of chemotherapy and died due to pneumonia and sepsis.     

Two-year survivor in response to gemcitabine-based chemotherapy for advanced pancreatic cancer with multiple lung metastases

A 65-year-old woman was admitted to our hospital for appetite loss and jaundice. Abdominal CT scan and ultrasonography both revealed a tumor in the head of the pancreas. Chest CT scan showed multiple nodules in both lungs. The patient was diagnosed as having advanced pancreatic cancer with multiple lung metastases. The primary tumor showed a partial response to the administration of gemcitabine 1,000 mg/m2 on days 1, 8 and 15 of a 28-day cycle. Concurrent treatment with 5-fluorouracil (200 mg/day) was efficacious against the lung metastases. One year later the pancreatic and lung tumors had enlarged, and cisplatin (20 mg/body) was added to the protocol. For 20 months the patient was treated as an outpatient, maintaining good quality of life. The patient died of progressive disease 25 months after her first hospital admission.     

Carcinomatous meningitis from non-small-cell lung cancer responding to gefitinib

The prognosis for carcinomatous meningitis remains poor, and focal neurological dysfunctions usually do not improve despite the available treatment options. We report a case of carcinomatous meningitis from non-small-cell lung cancer treated with gefitinib, which brought about a sustained clinical response. A 40-year-old Japanese man was diagnosed with adenocarcinoma in the right lower lobe of the lung, and with multiple pulmonary and brain metastases. Six courses of carboplatin and paclitaxel chemotherapy and gamma-knife radiosurgery induced a near complete response in all lesions. However, 2 months later, cauda equina syndrome and left oculomotor paralysis from carcinomatous meningitis developed rapidly. Magnetic resonance imaging of the brain and spinal cord revealed the enhancement of leptomeningeal disseminations. The patient was treated with 250 mg/day gefitinib. All his neurological symptomatology disappeared within 2 weeks. The shrinkage of the leptomeningeal disseminations was confirmed by follow-up magnetic resonance imaging. The patient is currently doing well and is able to work. Cancer relapse was not observed at 4 months after the initiation of gefitinib. Although the survival benefit is controversial, gefitinib may have a role in the treatment of carcinomatous meningitis from non-small-cell lung cancer to improve neurological dysfunctions.     

Gefitinib (‘Iressa’, ZD1839) is active against brain metastases in a 77 year old patient

This report highlights the case of a symptomatic 77-year-old non-smoking female patient who was diagnosed with advanced non-small-cell lung cancer (NSCLC), metastatic to the liver and contralateral lung. After tumor progression in the liver and lung following polychemotherapy, multiple diffuse brain and cerebellar metastases were apparent. Oral treatment with the epidermal growth factor receptor tyrosine kinase inhibitor gefitinib (‘Iressa’) 250 mg/day resulted in progressive and durable symptom relief, and improvements in quality of life and performance status. Reductions in the size of the primary pulmonary tumor and brain, cerebellar, and liver metastases were observed. Furthermore, gefitinib was well tolerated with an absence of adverse events. These results provide evidence that oral gefitinib is active in patients with advanced NSCLC and central nervous system metastases. An erratum to this article is available at .     

Near Total Regression of Diffuse Brain Metastases in Adenocarcinoma of the Lung with an EGFR Exon 19 Mutation: A Case Report and Review of the Literature

We report the case of a woman with diffuse brain metastases from lung cancer who experienced total regression of the metastases under gefitinib treatment. The 58-year-old woman was referred to our hospital with a complaint of severe headache. A brain MRI revealed diffuse metastatic lesions in the cerebra and cerebellum. Adenocarcinoma of the lung with multiple brain metastases was diagnosed. The tumor was positive for an epidermal growth factor receptor (EGFR) exon 19 deletion mutation. She was treated with gefitinib 250 mg per day. One year later, the diffuse brain metastases had totally resolved. EGFR-tyrosine kinase inhibitor therapy could be a first-line treatment for patients with advanced adenocarcinoma of the lung with EGFR mutation, especially in those with brain metastases.     

A case of advanced hepatocellular carcinoma with lung and bone metastases effectively treated by orally administered UFT

A 52-year-old male underwent hepatic subsegmentectomy for hepatocellular carcinoma (HCC). Five months later, a recurrent tumor was found in the liver and transcatheter arterial embolization (TAE) was performed. However, recurrent tumors were growing rapidly with multiple lung and bone metastases. The titer of serum AFP was elevated to 896,095 ng/ml and the titer of serum PIVKA-II was elevated to 1294.5 AU/ml. The patient was treated by oral administration of UFT (600 mg/day). Two weeks later, his general condition was improved, and several months later, the liver tumor, multiple lung metastases and multiple bone metastases had almost disappeared. The titers of serum AFP and PIVKA-II were reduced to the normal range. He has maintained a good state of health for about four years now. This case suggests the clinical usefulness of UFT for advanced HCC.     

Synchronous bilateral retinal metastases from lung adenocarcinoma

Hematogenous retinal metastases from non-small cell lung cancer are rare, and are even more uncommonly observed bilaterally. Non-small cell lung cancer usually metastasizes to the liver, adrenal glands, lung, bone, central nervous system, and kidney. We report the case of a 41-year-old male patient with advanced lung adenocarcinoma heavily pretreated with polychemotherapy and palliative radiotherapy up to June 2003, when synchronous bilateral retinal metastases were diagnosed. The patient's prognosis was worsened by the onset of the retinal metastases and he died three months later.     

Ileal perforation induced by acute radiation injury under gefitinib treatment

Enteritis is one of the side effects of radiotherapy to the abdominal cavity. Radiation enteritis involves damage to mucous membranes in the acute phase and to stromal tissues in the late phase. Perforation of the intestine tends to occur in the late phase, and rarely in the acute phase. However, we describe here a case of intestinal perforation occurring in the acute phase after irradiation in a patient who received gefitinib treatment. Gefitinib, one of the epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), is widely used to treat non-small cell lung cancer (NSCLC) patients, but is simultaneously known to inhibit wound healing. We suspect that gefitinib may affect regeneration of the small intestinal mucosa injured by irradiation. A 76-year-old woman had NSCLC with metastases to the 5th lumbar, sacral, and right iliac bones. To control the pain from bone metastasis, anterior-posterior opposing portal irradiation (total 35 Gy) was started, and was completed over 22 days. On day 25 after starting radiotherapy, the patient began to take gefitinib. On day 35, she presented with acute peritonitis, and an emergency laparotomy was performed. The terminal ileum was affected by radiation enteritis and there were two pin-hole perforations. In the surgical specimen, no cancerous lesions were detected, and immunohistochemical staining of phosphorylated EGFR (pEGFR) was negative. pEGFR has an important role in mucous membrane repair after irradiation. Intestinal perforation in the acute phase of radiation enteritis may be associated with impaired mucosal repair mechanisms due to the use of an EGFR-TKI such as gefitinib, as evidenced by the absence of pEGFR.     

Detection of occult bone metastases of lung cancer with Fluorine‐18 fluorodeoxyglucose positron emission tomography

Accurate staging of cancer has a critical role in optimal patient management. Fluorine‐18 fluorodeoxyglucose positron emission tomography (FDG PET) is superior to CT in the detection of local and distant metastases in patients with non‐small cell lung cancer. Although Tc‐99 m methylene diphosphonate (MDP) bone scanning is well established in the evaluation of bone metastases, there are conflicting reports on the use of FDG PET in the evaluation of skeletal metastases. We report on a patient with locally advanced lung carcinoma in whom FDG PET accurately identified previously unsuspected widespread asymptomatic bone metastases (bone scan and X‐rays negative, confirmed on MRI). Assessment of glucose metabolism with FDG PET might represent a more powerful tool to detect bone metastases in lung cancer compared with conventional bone scans.     

Recurrent low- to intermediate-grade chondrosarcoma of the thumb with lung metastases: an objective response to trofosfamide

BACKGROUND: Low- to intermediate-grade chondrosarcoma is usually a slow-growing and highly chemotherapyresistant tumor type. CASE REPORT: The 76-year-old female patient presented with low- to intermediate-grade chondrosarcoma of the distal phalanx of the right thumb in 1993 and was treated with an excision of the carpometacarpal joint. Approximately 10 years later, the patient presented with recurrent local disease at the trapezoid bone, which was resected. Eight months later she presented with local recurrence at the carpal joint and lung metastases. Subsequently she was treated chemotherapeutically with pegylated liposomal doxorubicin as part of a clinical trial. Due to tumor progression after 2 cycles, she was switched to oral trofosfamide (150 mg daily). A follow-up CT scan after 8 months demonstrated a partial remission that was confirmed by a second scan after 9 months of treatment. The treatment was well tolerated. After 18 months of continued treatment, she was still in remission and on trofosfamide. CONCLUSION: Trofosfamide at a daily dose of 150 mg may be effective in low- to intermediate-grade chondrosarcoma.     

Rapid multidisciplinary therapy for an advanced lung cancer patient with severe tracheal stenosis resulting in long-term survival

A 61-year-old female was admitted to our hospital due to dyspnea and facial edema. A chest CT scan showed stenosis of the trachea and superior vena cava due to a tumor around the trachea. She underwent partial resection of the tracheal tumor via a rigid bronchoscope introduced into the trachea, and placement of a Dumon Y-stent. Undifferentiated non-small cell lung cancer was diagnosed. After airway management, she underwent cisplatin-based chemoradiotherapy and total 56 Gy stereotactic radiotherapy for the tumor. The tumor size was reduced by 40% immediately after chemoradiotherapy. Six months after the tracheal stent insertion, bone metastases were pointed out, and we changed the chemotherapy regimen to gefitinib. She has been in good condition without tumor growth for more than six years after tracheal stent insertion.     

Gastric phenotype signet-ring cell carcinoma of the stomach with multiple bone metastases effectively treated with sequential methotrexate and 5-fluorouracil

A 63-year-old woman presented with an abnormal serum alkaline phosphatase (ALP) level. Computed tomography (CT) scan of the abdomen and pelvis and radioisotope (RI) examination led to a strong suspicion of systemic bone metastatic tumors, although the origin was not known. Biopsies from bone metastatic lesions in the left ilium were performed under CT scan, and signet-ring cell carcinoma cells were detected pathologically. Also, a 0-IIc-like lesion was observed endoscopically in the stomach, and signet-ring cell carcinoma cells were also detected histologically. The patient's platelet (Plt) levels were reduced and slight bleeding from the gingiva was detected when she brushed her teeth. Both the stomach and the bone metastatic lesions exhibited a gastric phenotype (G type) phenotypically. From these findings, we diagnosed the patient as having advanced (inoperable) stomach cancer with multiple bone metastases; she also exhibited disseminated intravascular coagulation (DIC). We treated her with sequential methotrexate and 5-fluorouracil (sequential MTX/5-FU) therapy after obtaining her informed consent. After six cycles of the chemotherapy, the abnormal ALP and Plt levels were alleviated. At present, she is receiving weekly sequential MTX/5-FU therapy at the outpatient oncology unit; she has been receiving the therapy for about 7 months since the detection of the bone metastases and has had a total of 17 cycles. In conclusion, sequential MTX/5-FU therapy was effective for a patient with G-type signet-ring cell carcinoma of the stomach with bone metastases, suggesting that the phenotypic classification may be one of the useful markers for prediction of the effectiveness of chemotherapy in patients with inoperable advanced stomach cancer.     

18F-FDG SPECT/CT与99mTc-MDP骨显像在检测肺癌骨转移中的对比研究

目的对比研究双探头符合线路SPECT/CT仪18F-脱氧葡萄糖(FDG)显像和99mTc-亚甲基二膦酸盐(MDP)显像对肺癌骨转移病灶的诊断效能。方法肺癌患者56例,分别行18F-FDGSPECT/CT胸腹部显像和99mTc-MDP全身骨显像,间隔时间不超过2周。结果56例患者中24例有骨转移,共发现92个转移灶;18F-FDGSPECT/CT检查发现68个转移灶,探测骨转移灶的灵敏度73.9%,特异性94.1%,准确率为81.1%;99mTc-MDP全身骨显像发现82个转移灶,探测骨转移灶灵敏度89.1%(P<0.01),特异性为72.5%(P<0.05),准确率为83.2%(P>0.05)。当把骨骼转移性病变以成骨性与溶骨性方式分类时,99mTc-MDP骨显像可判定94.3%的成骨性转移灶和82.1%的溶骨性转移灶,而18F-FDGSPECT/CT可判定58.5%的成骨性转移灶和94.9%的溶骨性转移灶。结论探测肺癌骨转移,18F-FDGSPECT/CT显像具有较高的特异性,99mTc-MDP骨显像具有较高的灵敏度,两者诊断的准确性无明显差异。99mTc-MDP骨显像联合18F—FDGSPECT/CT显像检测肺癌骨转移,可起到信息互补、明确诊断的作用。