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PubMed1996

Somatostatin receptor imaging: predictive and prognostic considerations.

Compared with other imaging modalities and clinical investigation, the 111In-pentetreotide scan identified additional metastatic disease sites in 12 carcinoid patients and 2 occult primaries, and influenced the therapeutic outcome in 36 patients [29 carcinoids, 2 atypical carcinoids, 3 cancers of unknown primaries (CUPs) and 2 medullary thyroid carcinomas (MCTs)]. No adverse reactions were noted. Somatostatin receptors were detected in 59/60 carcinoid patients, 3/4 atypical carcinoid patients, 0/2 MCT patients, and 0/3 cases of CUP. Somatostatin receptor presence is underestimated in some patients using standard hormonal response criteria rather than scintigraphy. 18 patients with metastatic carcinoids who underwent 111In-pentetreotide scanning were all somatostatin receptor positive. Their mean (+/- SE) 5-hydroxyindoleacetic acid (5-HIAA) suppression with octreotide therapy was -53% (+/- 6%). 8 patients had < 50% and 10 had > 50% 5-HIAA suppression (ranges: -4 to -47% and -58 to -94%, respectively). To investigate the effect of somatostatin analogues on survival, 90 consecutive cases of carcinoid syndrome patients treated during the somatostatin analogue era were reviewed. Survival according to primary site was 12.01, 18.29 and 6.05 years (overall median 12.01 years) for patients with foregut, midgut and unknown primaries, respectively. The difference from historical controls is substantial (67 vs. 18% 5-year survival), although our series is neither prospective nor randomised. The heterogeneity in patient and tumour response to somatostatin analogue therapy is discussed.

Carcinoid Tumor↗
PubMed1998

[Carcinoma of unknown primary site. Apropos of 100 patients treated at the Montpellier regional center of cancer prevention].

PURPOSE: Carcinomas of unknown primary site are frequent neoplasms which raise diagnostic and therapeutic problems in clinical practice. METHODS: Clinical records of 100 patients with carcinoma of unknown primary site whose clinical management took place at the Centre Regional de Lutte Contre le Cancer de Montpellier were retrospectively reviewed. Initial clinical and biological characteristics, pre-treatment evaluation, therapies and outcome were recorded. RESULTS: Three main histological types were observed: adenocarcinoma (66 patients), poorly differentiated carcinoma (19 patients), epidermoid carcinoma (11 patients). Bone, lung, lymph nodes and liver were the most frequently involved metastatic sites. Analysis of the investigations aimed at identifying the primary site (none of which being positive) showed 68 different combinations in 100 patients. Anemia (< 100 g/L) was observed in 10 patients, while serum alkaline phosphatase was increased in 42 patients. Seven patients died before any therapy. Chemotherapy or radiotherapy was advocated in 70 and 59 patients, respectively. Thirty-six patients had concomitant chemoradiotherapy. Chemotherapy included a platinum derivative in 53 patients. The median number of cycles was four. Nine objective responses were observed, six of which occurred in patients who were receiving platinum-based chemotherapy. Ninety-six deaths were encountered, 95 due to the disease progress and one due to an intercurrent cause. The median survival was 9 months. Univariate analysis identified two prognostic factors: the number of metastatic sites and the serum alkaline phosphatase. CONCLUSIONS: This retrospective study confirms the difficulties in the management of patients with carcinomas of unknown primary site. A literature review suggests limited diagnostic investigations in clinical practice with the aim of identifying tumors of potential prognostic (breast and ovary) or therapeutic (prostate) value. Apart from specific subgroups of patients for whom specific therapy is recommended, there is no current standard chemotherapy.

Adenocarcinoma↗
PubMed1984

[Brain metastases as primary manifestation of non-small cell bronchogenic carcinomas].

While brain metastases from small cell lung cancer are a familiar problem, the incidence of brain metastases from non-small cell lung cancer, and their significance as the first tumor manifestation, has been underestimated. At the University Hospital, Basle, over one year, 7 (approximately 7%) of 102 patients with newly diagnosed non-small cell lung cancer had brain metastases as the first manifestation of systemic cancer. Three of the 7 patients were women with a mean age of 48 years. Initial symptoms were headaches, vertigo and vomiting, which prompted the diagnosis of brain metastases. In only 3 patients was the primary lung cancer diagnosed immediately after diagnosis of the brain metastases, while in the remaining 4 a period of up to 6 months elapsed. Bronchogenic cancer is the most frequent primary in patients presenting with brain metastases. Accordingly, in a patient with brain metastases from an unknown primary, bronchogenic cancer should be considered first and diagnostic tests aimed in that direction. This may obviate an extended and expensive diagnostic workup.

Adult↗
PubMed1985

Cost-effectiveness in the diagnosis and treatment of carcinoma of unknown primary origin.

Between 2% and 9% of patients with cancer present with metastatic nonsquamous cell carcinoma of unknown primary origin. Traditionally, a series of investigations is undertaken to locate the primary origin of the tumour, although many of these tests are often painful or distressing to patients, unsuccessful in locating the primary site and costly to the health care system. Moreover, even if a tumour is found it usually cannot be treated surgically. However, a small number of cancers of unknown primary origin can be cured, arrested or effectively palliated with systemic treatment. This study compares the costs and outcomes of the current practice of comprehensively searching for the primary tumour with those of an alternative, limited approach that identifies only the primary tumours for which relatively effective systemic therapy exists. Decision trees were constructed for the two diagnostic approaches and their associated therapeutic options. Costs and probabilities were integrated with published data on the survival of patients with each type of cancer. The results indicate that the comprehensive diagnostic strategy may increase 1-year survival rates from 11.0% to 11.5%. On the basis of Ontario cost data it is calculated that the additional costs of a comprehensive search for 1000 patients will range from approximately $2 million to $8 million, depending on the subsequent treatment strategy.

Carcinoma↗
PubMed1998

Irinotecan in lymphoma, leukemia, and breast, pancreatic, ovarian, and small-cell lung cancers.

Irincotecan (CPT-11 [Camptosar] has a board range of antitumor activity. Extensive preclinical and early clinical work has demonstrated its activity against many tumor types--head and neck, esophagus, stomach, pancreas, liver, colon/rectum, kidney, lymph nodes, ovary, uterine, cervix, sarcoma, melanoma, acute and chronic leukemia, mesothelioma, and cancers of unknown primary site. Most of the phase II and III trials have focused on colorectal and other gastrointestinal, non-small-cell lung, and cervical cancers (discussed elsewhere in this monograph). This article presents preliminary results of studies exploring the use of irinotecan in lymphoma, leukemia, and breast, pancreatic, ovarian, and small-cell lung cancers. In all of these studies, the number of patients enrolled is small, drug doses and schedules differ (often within the same case series), and little information is available on response duration and overall survival. Nevertheless, irinotecan has shown reproducible if at times modest activity in almost all of the diseases in which it has been studied. Future research should be directed at conducting well-designed clinical trials of irinotecan alone and in combination with other agents.

Animals↗
PubMed1995

Massive metastases from a lobular breast carcinoma from an unknown primary during pregnancy. A case report.

BACKGROUND: Carcinoma of the breast during pregnancy represents 2-5% of all breast cancers. The frequency and histopathologic spectrum of breast cancer are similar in pregnant and nonpregnant women. Infiltrating lobular carcinoma is one of the less understood types of breast cancer, and its metastatic pattern seems to be different from that of infiltrating ductal carcinoma. Breast neoplasms rarely present as cancer from an unknown primary site. CASE: A woman in the third trimester of pregnancy developed carcinoma massively metastatic to the bone marrow and liver from an unknown primary tumor. At 32 weeks' gestation a healthy male was delivered by cesarean section. The patient died 12 hours after delivery. The autopsy revealed an infiltrating lobular carcinoma, 1.5 cm, of the breast. CONCLUSION: Massive metastases from an occult lobular breast carcinoma in a pregnant woman are very rare. Diffuse metastatic spread, which often complicates or delays the diagnosis, is a characteristic pattern of infiltrating lobular carcinoma. Cancer from an unknown primary site during pregnancy is an exceptional finding. If a metastatic adenocarcinoma is diagnosed in a pregnant woman, a breast primary should be strongly suspected.

Adult↗
PubMed2005

Diagnostic utility of positron emission tomography-computed tomography for predicting malignancy in cystic neck masses in adults.

OBJECTIVES: Combined positron emission tomography and computed tomography (PET-CT) is used for the diagnostic evaluation and staging of squamous cell carcinoma of the head and neck (SCCHN). By superimposing anatomic localization of CT with the physiologic data of PET, occult primary and metastatic neoplasms might be identified. Because the diagnostic algorithm for cystic neck masses in adults often overlaps with the work-up of cancer of unknown primary site, we evaluated the utility of PET-CT scans to identify the presence of malignancy and the location of primary tumor. STUDY DESIGN: Single-institution retrospective case review series. METHODS: We reviewed the PET-CT imaging of cystic neck masses occurring in five patients over 40 years of age with significant risk factors for SCCHN and correlated this information with histopathology. RESULTS: In each patient in our series, the PET portion of a combined PET-CT was misleading, whereas the CT examination was more suggestive of the correct pathology. Ultimately, clinical judgment and endoscopic evaluation, guided by CT findings, were most valuable for distinguishing malignant versus benign processes and identifying the primary tumor sites. CONCLUSIONS: PET-CT may not be a reliable modality for identifying malignancy in adults with suspicious cystic neck masses. A thorough clinical evaluation by an experienced head and neck surgeon, in conjunction with contrast-enhanced CT, may be sufficient to facilitate the optimal management of such patients.

Adult↗
PubMed1996

Regional perfusion with hemofiltration (chemofiltration) for the treatment of patients with regionally advanced cancer.

BACKGROUND: Regionally advanced cancer is a common, often unresolved problem. Effective local control with chemotherapy is limited by the toxicity following systemic administration. Chemofiltration (CF) is a form of regional perfusion that enables the administration of cytotoxic drugs into one body area while limiting systemic toxicity. The drug is infused into the artery supplying the involved area. The venous effluent of the same organ is pumped out into a hemofiltration unit at a high flow rate. The drug is then filtered away and the blood returned to systemic circulation. METHODS: Forty-one patients underwent 45 CF. Twenty-four patients had CF of the pelvis for advanced rectal carcinoma (10), malignant melanoma (6), and cancers of the uterine cervix (3), ovary (2), vulva (1), endometrium (1), and anus (1). Seventeen patients underwent CF of the liver for metastatic colon (10), breast (4), pancreas (1), ovary (1), and unknown primary (1) cancer. 5-fluorouracil (1 g/m2) and mitomycin-C (30 mg/m2); cisplatinum (200 mg/m2) alone or combined with bleomycin (50 mg/m2) and mitomycin-C (20 mg/m2); or melphalan (1 mg/kg) were the combinations used. RESULTS: Generally the procedure was well tolerated. Complications included transient leukopenia (18), paralytic ileus (2), hair loss (2), renal failure (1). Two patients died within 40 days following CF. Of 36 evaluable patients, 16 (44%) had partial response, 14 (38%) had stable disease, and 6 (18%) had disease progression. A decrease of at least 30% in carcinoembryonic antigen levels occurred in 12 of 24 patients (50%). Median time to progression was 7 months. Ten of 13 patients (77%) achieved good symptomatic palliation. CONCLUSIONS: The results of CF in our study are not superior to alternative methods of drug delivery to the liver and pelvis. However, considering that previous systemic chemotherapy had failed two-thirds of the patients, some benefit may be attributed to this regional delivery modality. Furthermore, pelvic CF afforded very significant symptomatic relief which was definitely superior to other methods.

Adult↗
PubMed1991

Cancer incidence in New South Wales, Australia.

In 1972, cancer registration began in New South Wales (NSW), the most populous state in Australia. The operations of the Registry are described. By 1990, approximately 316,000 new cases of cancer had been notified from a population that had increased from 4.6 to 5.8 million. In 1981-1984, the most common sites in men were lung, prostate, colon, melanoma and bladder, and in women, breast, melanoma, colon, lung and unknown primary site. Cancers which, between 1973-1976 and 1981-1984, had increased in reported incidence by more than 25% were pharynx and kidney in both sexes, rectum, testis and melanoma in men, and lung and bladder in women; those decreasing by more than 10% were stomach in both sexes, oesophagus in men and cervix in women. Age-standardised incidence rates for melanoma (27.4 [m] and 23.8 [f] per 100,000 in 1987) and cancer of the renal pelvis in women (1.7 per 100,000 in 1989) are among the highest in the world.

Age Factors↗
PubMed1998

A novel approach to microcalcification detection using fuzzy logic technique.

Breast cancer continues to be a significant public health problem in the United States. Approximately, 182,000 new cases of breast cancer are diagnosed and 46,000 women die of breast cancer each year. Even more disturbing is the fact that one out of eight women in the United States will develop breast cancer at some point during her lifetime. Since the cause of breast cancer remains unknown, primary prevention becomes impossible. Computer-aided mammography is an important and challenging task in automated diagnosis. It has great potential over traditional interpretation of film-screen mammography in terms of efficiency and accuracy. Microcalcifications are the earliest sign of breast carcinomas and their detection is one of the key issues for breast cancer control. In this study, a novel approach to microcalcification detection based on fuzzy logic technique is presented. Microcalcifications are first enhanced based on their brightness and nonuniformity. Then, the irrelevant breast structures are excluded by a curve detector. Finally, microcalcifications are located using an iterative threshold selection method. The shapes of microcalcifications are reconstructed and the isolated pixels are removed by employing the mathematical morphology technique. The essential idea of the proposed approach is to apply a fuzzified image of a mammogram to locate the suspicious regions and to interact the fuzzified image with the original image to preserve fidelity. The major advantage of the proposed method is its ability to detect microcalcifications even in very dense breast mammograms. A series of clinical mammograms are employed to test the proposed algorithm and the performance is evaluated by the free-response receiver operating characteristic curve. The experiments aptly show that the microcalcifications can be accurately detected even in very dense mammograms using the proposed approach.

Breast Neoplasms↗
PubMedDate not supplied

[Liver metastases with unknown primary site].

Patients with unknown primary site cancer represents 5% to 10% of all neoplasia patients. Liver is a favourite site for gastrointestinal tumors, but not only. The adenocarcinomas represents 60% of patients from this group. A detailed physical examination, extensive laboratory and imaging procedures are necessary to locate the primary tumor. However, liver biopsy could be essential for histological diagnosis and important to identify the tumors who may benefit from specific and effective therapy (breast cancer, prostate cancer, ovarian cancer and small-cell carcinoma of the lung). Systemic chemotherapy represents the most frequently treatment, but only patients with good performance status and without co-morbidities may benefit. "Best supporting care" may be the optimal treatment for most patients, majority with poor performance status at the time of diagnosis.

Adenocarcinoma↗
PubMed2024

Deep-Learning Model for Tumor-Type Prediction Using Targeted Clinical Genomic Sequencing Data.

UNLABELLED: Tumor type guides clinical treatment decisions in cancer, but histology-based diagnosis remains challenging. Genomic alterations are highly diagnostic of tumor type, and tumor-type classifiers trained on genomic features have been explored, but the most accurate methods are not clinically feasible, relying on features derived from whole-genome sequencing (WGS), or predicting across limited cancer types. We use genomic features from a data set of 39,787 solid tumors sequenced using a clinically targeted cancer gene panel to develop Genome-Derived-Diagnosis Ensemble (GDD-ENS): a hyperparameter ensemble for classifying tumor type using deep neural networks. GDD-ENS achieves 93% accuracy for high-confidence predictions across 38 cancer types, rivaling the performance of WGS-based methods. GDD-ENS can also guide diagnoses of rare type and cancers of unknown primary and incorporate patient-specific clinical information for improved predictions. Overall, integrating GDD-ENS into prospective clinical sequencing workflows could provide clinically relevant tumor-type predictions to guide treatment decisions in real time. SIGNIFICANCE: We describe a highly accurate tumor-type prediction model, designed specifically for clinical implementation. Our model relies only on widely used cancer gene panel sequencing data, predicts across 38 distinct cancer types, and supports integration of patient-specific nongenomic information for enhanced decision support in challenging diagnostic situations. See related commentary by Garg, p. 906. This article is featured in Selected Articles from This Issue, p. 897.

Humans↗
PubMed2026

HPV circulating tumor DNA as a potential prognostic and predictive biomarker in head and neck squamous cell carcinoma: a systematic review.

PURPOSE: Human papillomavirus circulating tumor DNA (HPVctDNA) has emerged as a promising prognostic biomarker in HPV-related head and neck squamous cell carcinoma (HNSCC). This systematic review aimed to synthesize current evidence on the diagnostic accuracy and prognostic value of HPVctDNA in HNSCC management. MATERIAL/METHODS: We systematically reviewed a PubMed-indexed database of studies published between January 2012 and September 2025. Eligible studies were assessed for design, primary tumor site and stage, treatment modality, HPVctDNA detection method, diagnostic accuracy (sensitivity and specificity), and reported clinical endpoints. Descriptive syntheses were performed; sensitivity and specificity were standardized to proportions and summarized as median values per group. RESULTS: A total of 60 studies, including 8,234 patients were analyzed, of which 41 (68.3%) focused exclusively on oropharyngeal squamous cell carcinoma (OPSCC) and 17 (28.3%) included mixed HPV-related HNSCC subsites and HPV-positive cancers of unknown primary. The median follow-up across the included studies was 23&#xa0;months. Among the included studies, 19 were retrospective (31.7%) and 33 were prospective (55.0%), with a small proportion of cross-sectional and randomized clinical trials. Overall, 40 (66.7%) evaluated the role of HPVctDNA in a curative setting. Plasma was the most common sample type, analyzed in 55 studies (91.7%), while 5 studies also included saliva. Detection methods varied: 40 employed droplet digital PCR (ddPCR), 16 used quantitative PCR (qPCR) and 4 applied NGS-based assays. Most of these studies (38, 63.3%) evaluated the prognostic utility of HPVctDNA, while only 4 (6.7%) assessed HPVctDNA in a screening or diagnostic setting. Regarding diagnostic accuracy, the median sensitivity across evaluable studies was 91.1%, while the median specificity was 99.4%. In OPSCC-only cohorts, the median sensitivity and specificity were 89.4% and 99.4%, respectively. Dynamic changes in HPVctDNA levels during or after treatment were consistently associated with outcomes: clearance or sustained negativity correlated with higher response rates, improved progression-free survival and overall survival, while persistent positivity or increasing levels predicted disease progression and recurrence. CONCLUSIONS: HPVctDNA demonstrates high diagnostic and prognostic accuracy in HPV-related HNSCC, especially OPSCC, supporting its use for prognosis, treatment monitoring and early detection of recurrence. However, prospective interventional studies are still required to demonstrate that HPVctDNA-guided treatment decisions improve clinical outcomes before routine implementation.

Humans↗
PubMed1996

Tumor-associated hypereosinophilia: report of four cases.

Hypereosinophilia is a rare manifestation of cancer. We reported four cases of tumor-associated hypereosinophilia. These cases presented with peripheral hypereosinophilia and disseminated metastatic malignancies. All cases were male, including two cases with cancer of unknown primary site, one with hepatocellular carcinoma, and one with a liver tumor. The age ranged from 27 to 55 years. They all had liver involvement. Two cases had bone marrow metastases. The leukocyte counts ranged from 78,600/microliters to 190,000/microliters. The percentage of eosinophils ranged from 20% to 77%. The eosinophil counts ranged from 15,720 to 126,350/microliters with a mean of 74,700/microliters. The first three cases died within 8 days after the malignancies were pathologically confirmed. We suggest that peripheral hypereosinophilia is a poor prognostic sign which is frequently associated with disseminated cancer.

Adult↗
PubMed1992

Activity of topotecan, a new topoisomerase I inhibitor, against human tumor colony-forming units in vitro.

BACKGROUND: Topotecan [(S)-9-dimethylaminomethyl(10-hydroxy-camptothecin), NSC 609699, SK&F 104864A], a semisynthetic analogue of the natural product camptothecin, is a cell cycle-specific drug that exerts antineoplastic activity through inhibition of topoisomerase I. Currently, topotecan is undergoing phase I and early phase II clinical trials. The dose-limiting toxicity for topotecan is myelosuppression. PURPOSE: Our purpose was to determine plasma concentrations and exposure times necessary for optimal clinical activity and tumor types that may be responsive in phase II clinical studies of topotecan. METHODS: A soft-agar cloning system assay was used to determine the in vitro effects of topotecan against cells from biopsy specimens of colorectal, breast, lung, ovarian, renal cell, and gastric cancers and cancers of unknown primary origin. We studied 141 freshly explanted tumor specimens, using 1-hour exposure to topotecan, and 80 were studied using continuous exposure. A decrease in tumor colony formation resulting from drug exposure was considered an in vitro response if survival of colonies was up to 50% of that in controls. RESULTS: With 1-hour exposure, in vitro responses were seen in 10% and 25% of assessable tumor specimens at final topotecan concentrations of 1.0 and 10.0 micrograms/mL, respectively. With continuous exposures at concentrations of 0.1 and 1.0 micrograms/mL, in vitro response rates were 34% and 76%, respectively. Specific activity was seen against colorectal, breast, non-small-cell lung, ovarian, and renal cell cancers, with responses observed in 27%, 25%, 32%, 39%, and 83%, respectively, of assessable tumor specimens after continuous exposure to 0.1 micrograms/mL topotecan. A subset of tumor specimens resistant to doxorubicin or fluorouracil was sensitive to topotecan, and the difference in sensitivity was statistically significant. In addition, some of the tumor specimens resistant to cyclophosphamide and etoposide were also sensitive to topotecan. CONCLUSIONS: Topotecan appears to be active in vitro against a variety of human tumors, including a subgroup resistant in vitro to standard antineoplastic agents. If plasma levels of 0.1 micrograms/mL can be achieved for prolonged periods of time in ongoing clinical trials, topotecan should have substantial clinical activity. IMPLICATIONS: Further clinical development of topotecan is warranted.

Antineoplastic Agents↗
PubMed2006

Iliac lymph node metastasis of an unknown primary tumor: report of a case.

Metastasis to the lymph nodes around the iliac vessels from cancer of an unknown primary (CUP) tumor has not yet been reported in either the English or Japanese literature and it is therefore described herein for the first time. The patient was a 70-year-old woman with persistent right leg edema. Computed tomography (CT) displayed a mass around the iliac vessels while physical, laboratory, and other imaging examination did not show any other tumor. Preoperatively diagnosed as a retroperitoneal tumor, the patient underwent a tumor resection, but a histopathological examination revealed the tumor to be poorly differentiated squamous cell carcinoma. Only residual lymph nodes in the pelvis were detected by postoperative fluorine-18 fluorodeoxyglucose-positron emission tomography. Neither a primary lesion nor any signs of recurrence were demonstrated for 13 months after radiotherapy for the residual nodes. We herein discuss the diagnosis, treatment, and follow-up of this less common CUP.

Aged↗
PubMed2006

Phase I trial of continuous infusion 9-aminocamptothecin in patients with advanced solid tumors: 21-day infusion is an active well-tolerated regimen.

This study's objectives were to determine the maximum tolerated dose (MTD) of 9-aminocamptothecin (9-AC), given as a prolonged continuous infusion (CI) for 7-21 days, when formulated in dimethylacetamide/polyethylene glycol 400 (DMA) and then later as a colloidal dispersion (CD), and to determine the steady-state pharmacokinetics of 9-AC. Patients with solid tumors refractory to standard therapy were enrolled on this study. Total dose/cycle of 9-AC/DMA was initially escalated by duration (7-21 days), while keeping the dose rate constant at 6.2 microg/m/h (1.04-3.12 mg/m/4-week cycle). Then, the dose rate was escalated from 6.2 to 21.1 microg/m/h (3.12-10.6 mg/m/4-week cycle) while keeping the infusion duration constant at 21 days. CD formulation was escalated from 14.1 to 25 microg/m/h (7.11-12.60 mg/m/4-week cycle) while keeping the infusion duration constant at 21 days and then escalated from 28.1 to 37.5 microg/m/h (9.44-12.60 mg/m/3-week cycle) while keeping the infusion duration constant at 14 days. Sixty-two patients were evaluable for toxicity; 61 received prior chemotherapy (median 3 regimens/patient). No consistent dose-limiting toxicity (DLT) was encountered with the DMA formulation until dose level 10.60 mg/m/cycle, when two patients experienced DLTs. With the 21-day CD formulation, the MTD was 12.60 mg/m/cycle with three DLTs out of five patients. When 9-AC was given on the 14-day schedule, DLT was seen at 9.44, 11.20 and 12.60 mg/m/cycle, with consistent DLT at the two highest dose levels. All DLTs for both formulations were grade 4 hematologic toxicities (neutropenia and/or thrombocytopenia), while non-hematologic toxicities were relatively mild (including gastrointestinal toxicities and fatigue). One patient with ovarian cancer had a complete response and three had partial responses (PRs). One patient each with non-Hodgkin's lymphoma and cancer of unknown primary had a PR. Pharmacokinetic studies of both formulations of 9-AC revealed a linear relationship between increasing plasma 9-AC lactone concentration and dose. The median plasma 9-AC lactone concentration for 9-AC/CD was approximately twice that achieved by 9-AC/DMA for the same dose level. Both 9-AC formulations, given as a 21-day CI, were well tolerated with dose-limiting myelosupression at the MTD. This dose intensity exceeds that of other 9-AC phase I/II schedules. The recommended phase II dose (RPTD) is 9.42 mg/m/4-week cycle, given as a 21-day infusion. The 14-day schedule of 9-AC/CD was equally myelosuppressive with the RPTD of 9.44 mg/m/3-week cycle, although two heavily pre-treated patients (one with pelvic radiotherapy) could not tolerate this dose. Objective responses were observed in six out of 57 heavily pre-treated patients, most of which had ovarian cancer.

Adult↗